concanavalin-a and Body-Weight

In infectious diseases and during inflammation, anorexia, loss of body weight, malaise, fatigue and depression are induced. These symptoms are correctively called 'sickness behaviors', and the central actions of cytokines play a role in their induction. The loss of body weight in cancer cachexia is also a result of development of sickness behaviors. It has been reported that the administration of NSAID ibuprofen to patients with cancer cachexia improves the loss in body weight. We studied the effect of NSAID on the loss of body weight by using rodent sickness behavior models. We have reported that sickness behaviors such as anorexia, decrease in body weight, and loss of locomotor activity are induced in concanavalin A (Con A)-induced mouse hepatitis and carbon tetrachloride-induced rat hepatitis. Zaltoprofen is a non-steroidal anti-inflammatory drug (NSAID) causes potent inhibition of cyclooxygenase-2 with fewer side effects on the gastrointestinal tract. Zaltoprofen improves the loss in body weight in both Con A-treated mice and carbon tetrachloride-treated rats. These results suggest the possible application of zaltoprofen for the treatment of sickness behaviors including loss of body weight occurring in cancer cachexia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzopyrans; Body Weight; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Concanavalin A; Mice; Propionates; Wasting Syndrome

A randomized, double-blind, placebo-controlled study was conducted to evaluate if Lactobacillus helveticus Lafti L10 (Lallemand Health Solutions, Montreal, Que., Canada) supplementation during 14 weeks in winter can influence the duration, severity, and incidence of upper respiratory tract illness (URTI), as well as to monitor different immune parameters in the population of elite athletes. Before and after the treatment, cardiopulmonary testing and self-rated state of moods evaluation (by Profile of Mood States questionnaire) were performed and blood samples were collected. Thirty-nine elite athletes were randomized either to the placebo (n = 19) or the probiotic (n = 20) group. The probiotic group received L. helveticus Lafti L10, 2 × 10(10) Colony Forming Units. Lafti L10 significantly shortened the URTI episode duration (7.25 ± 2.90 vs. 10.64 ± 4.67 days, p = 0.047) and decreased the number of symptoms in the probiotic group (4.92 ± 1.96 vs. 6.91 ± 1.22, p = 0.035). Severity and incidence of URTI did not differ between the treatments. There were no significant changes in leukocyte subpopulation abundance, transforming growth factor-β serum levels, level of interleukin-10 secreted from peptidoglican stimulated peripheral blood mononuclear cells (PBMCs), interferon-γ level secreted from concanavalin A-stimulated PBMCs or viability/proliferation of PBMCs upon antigen stimulation. Group effect for CD4+/CD8+ ratio was significant (F[1,37] = 6.99, p = 0.020, η(2) = 0.350); this difference was not significant at baseline, but was evident after 14 weeks (p = 0.02). A significant interaction effect was noted for self-rated sense of vigor (F[1,37] = 11.76, p = 0.009, η(2) = 0.595). Self-rated sense of vigor increased in the probiotic group (18.5 ± 4.1 vs. 21.0 ± 2.6, p = 0.012). Probiotic strain Lafti L10 can be a beneficial nutritional supplement for the reduction of URTI length in elite athletes.

Topics: Adolescent; Adult; Athletes; Body Mass Index; Body Weight; Cell Proliferation; Cell Survival; Concanavalin A; Double-Blind Method; Exercise; Female; Humans; Interferon-gamma; Interleukin-10; Lactobacillus helveticus; Leukocytes, Mononuclear; Male; Oxygen Consumption; Probiotics; Respiratory Tract Infections; Young Adult

The present study investigated the improving effect of cucurbitacin B on liver fibrosis induced by concanavalin A in mice and explored its possible mechanism. AST, ALT and TB were detected by kits. ELISA was performed to detect the levels of IL 5, IL 6, IL 13 and TNF-α in serum. Haematoxylin-eosin (HE) staining and Masson's trichrome staining were used to evaluate pathological changes. Western blotting was performed to observe expression levels of sirtuin (SIRT) 1, insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) and TGF β1. The activity of SIRT 1 also was detected. Results showed that cucurbitacin B could effectively improve the abnormal liver function, inhibit liver fibrosis and suppress releases of inflammatory factors in mice induced by concanavalin A. Furthermore, cucurbitacin B could down-regulate the expressions of TGF β1 and IGFBPrP1, increase the expression and activity of SIRT 1. Interestingly, when SIRT1 activity was inhibited by EX 527, a selective inhibitor of SIRT 1, the preventive effect of cucurbitacin B was significantly attenuated. Taken together, the above results showed that cucurbitacin B could significantly suppress releases of inflammatory cytokines and improve liver fibrosis induced by concanavalin A in mice, and those may be achieved through SIRT1/IGFBPrP1/TGF β1 axis.

Topics: Animals; Body Weight; Concanavalin A; Insulin-Like Growth Factor Binding Proteins; Interleukins; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; Sirtuin 1; Transforming Growth Factor beta1; Triterpenes; Tumor Necrosis Factor-alpha

Roots of Sophora flavescens is an important herbal medicine for treatment of HBV and hepatic carcinoma in China. Alkaloids in the root were well known for exhibiting good hepato-protective and anti-HBV effects. However, polysaccharides as main components in the root remained unknown. In the studies, we investigated the chemical features and hepatoprotective effects of Sophora flavescens polysaccharides (SFP-100 and its active fractions) with ConA-induced hepatitis mice, human liver LO2 cells and HepG2.2.15 cells. The results showed that SFP-100 was composed of arabinose, glucose, galactose and galacturonic acid, SFP-100-A mainly contained glucose. SFP-100-B and SFP-100-C were acidic polysaccharides. SFP-100 significantly decreased hepatocytes apoptosis, inhibited the infiltration of neutrophils and macrophages into liver, and improved the production of IFN-γ and IL-6 of splenocytes in ConA-induced hepatitis mice. SFP-100 and its two sugar fractions increased LO2 cell proliferation and reduced cell apoptosis induced by ConA. SFP-100, SFP-100-A and SFP-100-C remarkedly inhibited the secretion of HBsAg and HBeAg by HepG2.2.15 cells.These results suggested Sophora flavescens polysaccharides exerts significant hepatoprotective and anti-HBV roles, and further is used for treatment of immune-mediated liver disease in the future.

Topics: Animals; Antiviral Agents; Body Weight; Cell Proliferation; Cell Survival; Chemical and Drug Induced Liver Injury; Concanavalin A; Cytokines; Disease Models, Animal; Female; Hepatitis B; Hepatitis B virus; Hepatocytes; Lymphocytes; Mice; Organ Size; Plant Extracts; Plant Roots; Polysaccharides; Protective Agents; Sophora

Our previous study isolated an anti-fatigue polysaccharide (HRWP) from the Hippophae rhamnoides berry. In this study, using ion-exchange chromatography and gel filtration chromatography in turn, a water-soluble homogenous polysaccharide HRWP-A was isolated from HRWP. Structural analysis determined that HRWP-A was a polysaccharide with repeating units of (1→4)-β-d-galactopyranosyluronic residues, of which 85.16% were esterified with methyl groups. An antitumor activity assay showed that HRWP-A could significantly inhibit the Lewis lung carcinoma (LLC) growth in tumor-bearing mice. Further experiments suggested that the antitumor effect of HRWP-A might be mediated through immunostimulating activity, as it enhances the lymphocyte proliferation, augments the macrophage activities, as well as promoting NK cell activity and CTL cytotoxicity in tumor-bearing mice. To our knowledge, this is the first report on a natural antitumor high-methoxyl homogalacturonan pectin from the H. rhamnoides berry-a compound that acts as a potential immunostimulant and anticancer adjuvant.

Topics: Animals; Antineoplastic Agents; Body Weight; Carbon-13 Magnetic Resonance Spectroscopy; Carcinoma, Lewis Lung; Concanavalin A; Cytotoxicity, Immunologic; Fruit; Hippophae; Immunologic Factors; Killer Cells, Natural; Lipopolysaccharides; Macrophages; Male; Mice, Inbred C57BL; Nitric Oxide; Pectins; Phagocytosis; Proton Magnetic Resonance Spectroscopy; Spectroscopy, Fourier Transform Infrared; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factor-alpha

In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from plant or animal and used as a promising source of therapeutic agents for cancer. In this study, we examined the effects of Purslane polysaccharides (PPs) on the oxidative injury and immune status in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats. PPs administration (200, 400 or 800mg/kg body weight) could not only increase the body weight, peripheral white blood cells (WBC) count, thymus and spleen indexes, but also remarkably promote splenocytes proliferation of gastric cancer rats. Furthermore, the production of serum cytokines in gastric cancer rats, such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) was enhanced by PPs treatment. Besides, treatment with PPs was found to provide a dose-dependent protection against MNNG-induced oxidative injury by enhancing SOD, CAT, GSH-Px activities of gastric cancer rats. Taken together, we concluded that enhancement of antioxidants and immune response might be responsible for the anticancer effect of PPs in gastric cancer.

Topics: Animals; Antioxidants; Body Weight; Catalase; Cell Proliferation; Concanavalin A; Cytokines; Glutathione Peroxidase; Immunologic Factors; Leukocyte Count; Lipopolysaccharides; Male; Mice; Polysaccharides; Portulaca; Rats, Wistar; Spleen; Stomach Neoplasms; Superoxide Dismutase

Enhanced cruciferous vegetable consumption is associated with the reduction of cancer incidence as shown in epidemiological studies. Phenethyl isothiocyanate (PEITC), one of the important compounds in cruciferous vegetables, has been shown to induce apoptosis in many types of human cancer cell lines, but there is no available information addressing the effects on normal and leukemia mice in vivo. The purpose of this study is to focus on the in vivo effects of PEITC on immune responses of normal and WEHI-3 leukemia BALB/c mice in vivo. Influences of PEITC on BALB/c mice after intraperitoneal (i.p.) injection with WEHI-3 cells and normal mice were investigated. In normal BALB/c mice, PEITC did not affect the body weight when compared to the olive oil treated animals. Moreover, PEITC promoted phagocytosis by macrophages from peripheral blood mononuclear cells (PBMC) and peritoneal cavity, increased the levels of CD11b and Mac-3, decreased the level of CD19 and promoted natural killer (NK) cell cytotoxic activity, but it did not alter the level of CD3. Also, PEITC enhanced T cell proliferation after concanavalin A (Con A) stimulation. Otherwise, PEITC increased the body weight, but decreased the weight of liver and spleen as compared to the olive oil-treated WEHI-3 leukemia mice. PEITC also increased the level of CD19, decreased the levels of CD3 and Mac-3 rather than influence in the level of CD11b, suggesting that the differentiation of the precursor of macrophages and T cells was inhibited, but the differentiation of the precursor of B cells was promoted in leukemia mice. Furthermore, PEITC enhanced phagocytosis by monocytes and macrophages from PBMC and peritoneal cavity, and also promoted the NK cell cytotoxic activity in comparison with the group of leukemia mice. Based on these observations, the biological properties of PEITC can promote immune responses in normal and WEHI-3 leukemia mice in vivo. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Topics: Animals; B-Lymphocytes; Body Weight; Cell Line, Tumor; Concanavalin A; Cytotoxicity, Immunologic; Immunomodulation; Isothiocyanates; Killer Cells, Natural; Leukemia, Experimental; Leukocytes, Mononuclear; Liver; Lymphocyte Activation; Macrophages; Male; Mice; Mice, Inbred BALB C; Phagocytosis; Spleen; T-Lymphocytes

This study was designed to investigate the effects of dried plum on the changes in bone metabolism and the immune response associated with ovarian hormone deficiency. Adult female C57BL/6J mice were either sham-operated (Sham) and fed AIN-93 diet (control) or ovariectomized (OVX) and fed a control diet with 0%, 5%, 15% or 25% dried plum (w/w), corresponding to control, low- (LDP), medium- (MDP) and high (HDP)-dose dried plum. Four weeks of HDP supplementation prevented the decrease in spine bone mineral density and content induced by OVX. The OVX compromise in trabecular bone of the vertebra and proximal tibia was prevented by the higher doses of dried plum, and in the vertebra these effects resulted in greater (P<.05) bone strength and stiffness. In the bone marrow, OVX suppressed granulocyte and committed monocyte populations and increased the lymphoblast population, but the MDP and HDP restored these myeloid and lymphoid populations to the level of the Sham. Dried plum also suppressed lymphocyte tumor necrosis factor (TNF)-α production ex vivo by splenocytes, in response to concanavalin (Con) A stimulation. These data indicate that dried plum's positive effects on bone structural and biomechanical properties coincide with the restoration of certain bone marrow myeloid and lymphoid populations, and suppressed splenocyte activation occurring with ovarian hormone deficiency.

Topics: Animals; Biomarkers; Body Weight; Bone and Bones; Bone Density; Bone Marrow Cells; Concanavalin A; Cytokines; Dietary Supplements; Disease Models, Animal; Eating; Female; Femur; Gene Expression; Insulin-Like Growth Factor I; Mice; Mice, Inbred C57BL; Organ Size; Osteoporosis; Ovariectomy; Peptide Fragments; Procollagen; Prunus; Spleen; Tibia; Tumor Necrosis Factor-alpha; Uterus

The present study was conducted to investigate the effects of the diabetic condition on cytosolic free Ca(2+) concentration, [Ca(2+)](i), and the proliferation of splenic lymphocytes from mice. Diabetes was induced in mice by intraperitoneal injection of alloxan. [Ca(2+)](i) and the proliferation ex vivo of splenic lymphocytes isolated from mice were examined using fura-2 and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, respectively. Diabetes caused a significant increase in resting [Ca(2+)](i) and significantly reduced the ability of concanavalin A (Con A; a T-lymphocyte-selective mitogen) to increase [Ca(2+)](i), but not that of lipopolysaccharide (LPS; a B-lymphocyte-selective mitogen). In addition, diabetes significantly reduced Con A-stimulated but not LPS-stimulated lymphocyte proliferation. Verapamil (an L-type Ca(2+) channel blocker) inhibited Con A-induced increases in [Ca(2+)](i) and proliferation in lymphocytes from control and diabetic mice to a similar extent, respectively. These results suggest that diabetes attenuates Con A-stimulated T-lymphocyte proliferation by decreasing [Ca(2+)](i) via reduction of Ca(2+) entry through L-type Ca(2+) channels.

Topics: Animals; Blood Glucose; Body Weight; Calcium; Calcium Channels, L-Type; Concanavalin A; Diabetes Mellitus, Experimental; Fura-2; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes; Male; Mice; Spleen; Tetrazolium Salts; Thiazoles; Verapamil

Herbs, as food or medicine, can strengthen the body and increase its resistance to illnesses by acting on various components of the immune system. For example, Echinacea is noted for its ability to enhance immune function, primarily through activation of the innate immune responses. Here, we investigated the potential for two herbs commonly found in India, Ashwagandha (Withania somnifera) and Brahmi (Bacopa monnieri), to enhance immune function and compared their effects to that of Echinacea.. Sprague Dawley rats were fed a diet supplemented with 1% (w/w) Echinacea, Ashwagandha, or Brahmi for 4 weeks to examine their effects on immune function.. The Brahmi diet stimulated more secretion of IgA and IgG in the serum compared to Echinacea or Ashwagandha. Whether or not lectin was present in the diet, the production of IgA, IgG and IgM in spleen lymphocytes increased with herbal supplements. The concentrations of IFN-γ and IL-2 treated with LPS and ConA were significantly higher in the dietary herb than in the control. On the contrary, TNF-α production in rats receiving dietary herbal supplements was significantly lower compared to the control animals.. Herbal remedies based on Echinacea, Brahmi, or Ashwagandha can enhance immune function by increasing immunoglobulin production. Furthermore, these herbal medicines might regulate antibody production by augmenting both Th1 and Th2 cytokine production.

Topics: Administration, Oral; Animals; Bacopa; Body Weight; Cells, Cultured; Concanavalin A; Diet; Eating; Echinacea; Immunoglobulin A; Immunoglobulin G; Interferon-gamma; Interleukin-2; Lipopolysaccharides; Lymphocytes; Male; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Spleen; Tumor Necrosis Factor-alpha; Withania

We investigated the anti-inflammatory effects of minocycline in EAE, an animal model of MS. Minocycline, administered for two weeks after the clinical onset, significantly decreased the cumulative and mean clinical scores of EAE. This was associated with the reduction of both CD4(+) and CD8(+) T cell numbers in the spinal cord and the downregulation of LFA-1 on T cells without affecting the cytokine production profile. The predominant cytokine produced by T cells in the spleen was IFN-gamma whereas in the CNS it was IL-17. Our results indicate that minocycline regulates T cell infiltration into the CNS without modifying the dominant cytokine production.

Topics: Animals; Antigens, CD; Body Weight; Concanavalin A; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Flow Cytometry; Lymphocyte Function-Associated Antigen-1; Minocycline; Rats; Spinal Cord; T-Lymphocytes

Mesenchymal stem cells (MSC) are potent in immunomodulation. It has been proven that MSC functioned to correct immune disorder in several immune diseases. Here, we tested the hypothesis that MSC from human bone marrow (hMSC) can provide a potential therapy for experimental autoimmune myasthenia gravis (EAMG). EAMG mice model was established by subcutaneous injection of synthetic analogue of acetylcholine receptor (AchR), then, hMSC were intravenously delivered into these mice repeatedly. The results showed that hMSC could specifically home to spleen tissue and hMSC treatment significantly improved the functional deficits of EAMG mice. In addition, AchR antibody level was dramatically decreased in cell-treated group when compared with untreated control on 10 days after the second cell injection. Moreover, both in vivo and in vitro mixed lymphocyte proliferation assays revealed that hMSC could definitely inhibit the proliferation of AchR-specific lymphocyte. In conclusion, our study demonstrated that hMSC treatment was therapeutically useful in autoimmune myasthenia gravis mice, and the underlying mechanism may relate with their immunomodulatory potential.

Topics: Animals; Antibodies; Antigens, CD; Body Weight; Bone Marrow Cells; Cell Adhesion; Cell Differentiation; Cell Lineage; Cell Proliferation; Coculture Techniques; Concanavalin A; Culture Media, Conditioned; Epitopes, T-Lymphocyte; Female; Humans; Immunomodulation; Immunophenotyping; Injections, Intravenous; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphoid Tissue; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Myasthenia Gravis, Autoimmune, Experimental; Receptors, Cholinergic; Spleen; Transplantation, Heterologous; Treatment Outcome

Concanavalin A (Con A)-induced acute liver injury model is well established as a model of T cell-mediated liver injury, in which T cells and NKT cells exert their cytotoxicity towards liver cells. In this study, we investigated the protective effects of CGX, a traditional Korean medicine against Con A-induced liver injury and its underlying mechanisms. After pretreatment with CGX (po, 50, 100 or 200 mg/kg) or distilled water once daily during 7 days, Con A (15 mg/kg) was injected intravenously. Thereafter serum level of AST and ALT, lipid peroxidation and cytokines in the liver tissue, and immune cell population in blood and the spleen were analyzed. CGX treatment reduced serum ALT, AST level in a dose-dependent manner. CGX treatment significantly decreased the lipid peroxidation and glutathione depletion in the liver tissue, and also lowered tissue levels of tumor necrotic factor-α and interferon-γ. CGX treatment attenuated the compositional alteration of Tc, Th, NKT, and B cells in blood as well as in the spleen. These results suggest that CGX has hepatoprotective property against Con A-induced liver injury through antioxidant action and immune regulation.

Topics: Animals; Body Weight; Catalase; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Concanavalin A; Glutathione; Inflammation Mediators; Interferon-gamma; Liver; Liver Function Tests; Lymphocyte Subsets; Male; Malondialdehyde; Mass Spectrometry; Medicine, Korean Traditional; Mice; Mice, Inbred BALB C; Organ Size; Peptide Mapping; Plant Extracts; Spleen; Thymus Gland; Tumor Necrosis Factor-alpha

A study was conducted to investigate the effects of L-arginine (Arg) on performance and immune function in cyclophosphamide (CY) immunosuppressed weaned pigs. The weaned pigs were allotted randomly into one of three treatments, including: (1) non-challenged control; (2) CY-challenged group; and (3) CY + 0.5% Arg. On days 14 and 21 of the trial, pigs were injected with CY or sterile saline. Blood samples were obtained on days 21 and 28 of the trial for further analysis. On day 28, delayed-type hypersensitivity reaction was evaluated. Arg alleviated the decrease of average daily gain (P < 0.05) induced by CY challenge from days 21 to 28. Arg mitigated the CY-induced decrease of total white blood cell numbers (P < 0.05) on day 28 and improved the lymphocyte percentage on day 21 (P < 0.05). Arg increased the delayed-type hypersensitivity reaction (P < 0.05), and attenuated the decrease of bovine serum albumin antibody level caused by CY treatment (P < 0.05) on day 28. In addition, Arg elevated the levels of serum interleukin-2 and interferon-gamma (P < 0.05) on day 28, and mitigated the decrease of serum interferon-gamma level on day 21 (P < 0.05). These results indicate that Arg supplementation has beneficial effects in attenuating the immunosuppressive effects of CY challenge, therefore improving growth performance of young pigs.

Topics: Animals; Arginine; Blood Cell Count; Body Weight; Cell Proliferation; Concanavalin A; Cyclophosphamide; Dietary Supplements; Hypersensitivity, Delayed; Immune Tolerance; Immunoglobulin G; Immunosuppressive Agents; Interferon-gamma; Interleukin-2; Leukocytes, Mononuclear; Mitogens; Phytohemagglutinins; Sus scrofa; Weaning

Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because some agents used in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects coupled with low toxicity, we investigated the effect of Compound K (K), the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., either as a single treatment or combined with tacrolimus (FK-506) on acute cardiac allograft rejection. We compared the ability of K alone, or in combination with FK-506, to inhibit acute heart transplant rejection both in vitro and in vivo. We found that the inhibition of lymphocyte proliferation was positively correlated with K concentration. K significantly reduced IL-2 and IFN-gamma expression levels and significantly inhibited lymphocyte proliferation in both a lymphocyte transformation test and a mixed lymphocyte reaction (MLR). We also found that the inhibitory effect of a combination of K and a sub-therapeutic dose of FK-506 (SubFK-506) was stronger than that of full-dose FK-506 alone. Oral administration of K reduced acute cardiac allograft rejection in mice and had no apparent toxicity. In vivo, the immunosuppressive effect of K combined with a half-dose of FK-506 was equivalent to that of a full-dose of FK-506 alone. K combined with a half-dose of FK-506 reduced the expression levels of IL-2 and IFN-gamma (both within the graft and in the recipients' serum) more effectively than a full-dose of FK-506. These results show that K has significant immunosuppressive effects both in vitro and in vivo. When used as a combination therapy with FK-506 we see a powerful inhibition of rejection with no obvious toxic side effects. The mechanism of action is postulated to involve the inhibition of IL-2 and IFN-gamma expressions by lymphocytes, rather than the activation of Tr1 cells via the production of IL-10.

Topics: Animals; Body Weight; Cell Proliferation; Concanavalin A; Drug Synergism; Drugs, Chinese Herbal; Fatty Acids, Unsaturated; Female; Gene Expression; Graft Rejection; Graft Survival; Heart Transplantation; Immunosuppressive Agents; Interferon-gamma; Interleukin-10; Interleukin-2; Isatis; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes; Tacrolimus; Transplantation, Homologous

Manipulation of dietary variables is one the most described events to retard the aging process and maintain immune function. The present study deals with the effect of variable dietary protein-carbohydrate ratios (without caloric restriction) on the alteration of immune response of male albino rats at the level of lymphocyte viability, proliferation, cytotoxicity, DNA fragmentation of blood, spleen and thymus and corticosterone levels in plasma and adrenal gland in relation to aging and duration of dietary exposure. Young (3 months) and aged rats (18 months) maintained with control diet [protein (20%)-carbohydrate (68%)] showed age-induced decrease in immune response with an increase in plasma corticosterone level. Consumption of low protein (8%)-high carbohydrate (80%) (LP-HC) diet for short-term period (15 consecutive days) decreased immune response of young rats with little immunopotentiation of aged rats but prolongation of consumption (for 60 consecutive days) of the LP-HC diet potentiated these immunopotentiation effects. High protein (50%)-low carbohydrate (38%) (HP-LC) diet under short-term exposure contrarily showed little immunopotentiation in young with an immunosuppression in aged rats. Prolongation of exposure (for 60 consecutive days) to the HP-LC diet produced similar but more amplified effects in young rats; whereas, in aged rats a pronounced decrease in peripheral immune response with an activation in thymus-dependent immune response was observed under similar conditions. These results thus suggest that diets with variable dietary protein-carbohydrate ratios act as an exogenous modulator of immune response with age and LP-HC diet may be beneficial to slow down/reduce the impairment of immune response in aged individuals.

Topics: Aging; Animals; Body Weight; Cell Proliferation; Concanavalin A; Corticosterone; Cytotoxicity, Immunologic; Diet; Dietary Carbohydrates; Dietary Proteins; DNA Fragmentation; Lymphocyte Activation; Male; Rats; T-Lymphocytes

Chi-Shie-Shuang-Bu-An-Shen-Tang (CST), a traditional Chinese medicine, has long been used to stabilize one's spirit and treatment of body weakness caused by fatigue. In order to understand whether the CST possess the immunological function and effect of thermal processing on its activities, sterilized (SCST) and nonsterilized CST (NCST) extracts were orally administrated to BABL/c mice for 1 or 3 weeks as drinking water. The results showed that CST extract after sterilization at 121 degrees C for 15 min had higher immunological activities than nonsterilized CST. SCST revealed mitogenic effects on splenocyte stimulated by concanavalin A (Con A) and mediated the changes of total serum antibodies; production of IgG increased and IgE reduced. Among cytokines, secretion of IFN-gamma increased and IL-5 decreased, which fit in with the Th1 cell profile, however cytolytic activity of natural killer cells did not show any significant difference. Furthermore, the population of CD4(+) T cells in the mice spleen increased after oral administration of SCST for 3 weeks. These results suggest that SCST had the immunomodulatory effects which drove CD4(+) T cells into Th1 cells and had potential benefit to cope with CD4(+) T lymphopenia condition.

Topics: Administration, Oral; Animals; Body Weight; Cell Proliferation; Concanavalin A; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Immunoglobulin G; Immunoglobulin M; Immunologic Factors; Immunophenotyping; Interferon-gamma; Interleukin-2; Interleukin-5; Killer Cells, Natural; Lipopolysaccharides; Lymphocytes; Medicine, Chinese Traditional; Mice; Mice, Inbred BALB C; Mitogens; Plant Extracts; Spleen

Although concanavalin A (Con A) as a T cell stimulant can cause natural killer T (NKT) cell-mediated liver injury in mice and a nonhepatotoxic dose of Con A can trigger innate immune cells including NKT cells to prevent tumor metastasis in the liver, little is known about the role of Con A-primed NKT cells in liver repair. In this study, we aimed to investigate the effect of pretreatment with a nontoxic dose of Con A on subsequent liver regeneration in mice.. A nontoxic dose of Con A was injected intravenously 24 h before partial hepatectomy (PHx), which was used as a model of liver regeneration. Ratios of remnant liver mass to body weight, bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling were used to assess liver regeneration.. Hepatic mononuclear cells were isolated and analyzed by flow cytometry. After PHx, the ratios of liver weight to body weight, PCNA-positive hepatocytes and BrdU-positive hepatocytes in Con A-pretreated mice were significantly higher than that of phosphate-buffered saline-treated mice, indicating that Con A pretreatment can accelerate liver regeneration. Flow cytometric analysis showed that NKT cells were significantly activated and selectively eliminated after the Con A administration. Moreover, NKT cells expressed more apoptosis-related molecules, Fas and Annexin V.. Taken together, Con A accelerates liver regeneration in mice by eliminating hepatic NKT cells via activation-induced cell death.

Topics: Alanine Transaminase; Animals; Antimetabolites, Antineoplastic; Body Weight; Bromodeoxyuridine; Cell Death; Concanavalin A; Disease Models, Animal; Dose-Response Relationship, Drug; Flow Cytometry; Hepatocytes; Immunohistochemistry; Killer Cells, Natural; Liver Neoplasms; Liver Regeneration; Male; Mice; Mice, Inbred C57BL; Mitogens; Organ Size; Proliferating Cell Nuclear Antigen; T-Lymphocytes

EAN induced in Lewis rats by immunization with peripheral bovine myelin was treated by the Ras inhibitor farnesylthiosalicylate (FTS). Treatment from day 0 with FTS (5 mg/kg intraperitoneally twice daily) attenuated peak clinical scores (mean+/-S.E., 2.5+/-0.5 compared to 4.1+/-0.5 in saline treated controls, p=0.018, t-test) but not recovery. Treatment from day 10 with FTS attenuated peak disability (2.5+/-0.6, p=0.032 compared to saline treated controls) and improved recovery (0.84+/-0.42, untreated controls 2.4+/-0.6, p=0.028 by repeated measures ANOVA). Effects were confirmed by rotarod and nerve conduction studies. An inactive analogue, geranylthiosalicylate, had no clinical effect. Inhibition of Ras is of potential use in the treatment of inflammatory neuropathies.

Topics: Analysis of Variance; Animals; Behavior, Animal; Body Weight; Cell Proliferation; Cells, Cultured; Concanavalin A; Disease Models, Animal; Dose-Response Relationship, Immunologic; Drug Interactions; Electromyography; Enzyme Inhibitors; Farnesol; Female; Lymphocytes; Motor Activity; Mycobacterium tuberculosis; Myelin Proteins; Neural Conduction; Neuritis, Autoimmune, Experimental; ras Proteins; Rats; Rats, Inbred Lew; Rotarod Performance Test; Salicylates; Severity of Illness Index

Cytokines produced by Th1 or Th2 cells have been postulated to be important in the development of type 1 diabetes in humans and animal models, such as murine multiple low-dose streptozotocin (MLDSTZ)-induced diabetes. The aim of this study was to investigate cytokine production with or without in vitro depletion of plastic adherent cells from spleens isolated after MLDSTZ treatment. Spleen cells were prepared on day 14 from MLDSTZ- and saline-treated mice and divided into two fractions. One cell fraction was depleted of adherent cells by plastic adherence and the other was not. Both cell fractions were analysed by FACS for the distribution of immune cells. In other experiments, the cells were cultured for 48 h with concanavalin A stimulation. Supernatant samples were analysed by ELISA for TNFalpha, IFNgamma and IL-10 production. Either before or after the 48-h culture cytokine mRNA expression was determined by RT-PCR. Plastic adhesion decreased the macrophage numbers by approximately 30% and CD4(+)CD25(+) cells by about 60%. This was accompanied by increased medium levels of TNFalpha, IFNgamma and IL-10, which suggest that either CD4(+)CD25(+) cells, macrophages, or both, down-regulate production of both Th1 and certain Th2 cytokines. Depletion of adherent cells also decreased IL-4 mRNA amounts. MLDSTZ treatment increased the production of Th1 cytokines mainly at the protein level, and IL-10 mainly at the mRNA level. This indicates a sustained increase in Th1 production after MLDSTZ treatment and an increase in IL-10 that might reflect an attempt to counteract the MLDSTZ-induced immune damage. Plastic adhesion during cell preparation may affect the relative distribution of certain immune cells.

Topics: Animals; B-Lymphocytes; Blood Glucose; Body Weight; Cell Adhesion; Cell Count; Concanavalin A; Cytokines; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Gene Expression; Interferon-gamma; Interleukin-10; Interleukin-4; Macrophages; Male; Mice; Mice, Inbred C57BL; Plastics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spleen; Streptozocin; T-Lymphocyte Subsets; Th1 Cells; Th2 Cells; Tumor Necrosis Factor-alpha

This study examined the influence of a low level of dietary lectin (0.34%), at a dose that did not affect body weight or food intake, on the concentration of serum cholesterol and fecal excretion of neutral sterols in rats fed a diet containing 0.50% cholesterol and 0.13% sodium cholate for 12 d. In experiment 1, rats fed a diet with 0.34% lectin, concanavalin A, had significantly lower concentrations of serum total cholesterol and hepatic cholesterol, a higher ratio of HDL-cholesterol to total cholesterol, enhanced excretion of fecal neutral sterols and reduced apparent cholesterol absorption or digestibility as compared with rats fed a diet without lectin. Fecal excretion of acidic sterols was unaffected by dietary lectin. In contrast, dietary 0.34% lectin had no significant effect on concentrations of serum total protein or glucose. In experiment 2, we examined whether the cholesterol-lowering activity of the lectin was responsibility for its carbohydrate-binding activity. The effect of dietary lectin on concentrations of serum and hepatic cholesterol and excretion of fecal neutral sterols was prevented by simultaneous administration of methyl-alpha-D-mannopyranoside with specific affinity for the carbohydrate-binding sites of the lectin. These results suggest that dietary lectins might reduce concentrations of serum and hepatic cholesterol by a mechanism involving higher excretion of neutral sterols and that these alterations might be associated with the carbohydrate-binding activity of lectin.

Topics: Animals; Anticholesteremic Agents; Body Weight; Carbohydrate Metabolism; Cholesterol; Cholesterol, Dietary; Concanavalin A; Dietary Supplements; Eating; Feces; Intestinal Absorption; Lipids; Liver; Male; Methylmannosides; Rats; Rats, Wistar; Sterols

Placenta immunomodulatory ferritin (PLIF) cDNA was recently cloned from the human placenta, where it is expressed in syncytiotrophoblast and decidual mononuclear cells. PLIF and its subcloned bioactive domain (C48), expressed in Escherichia coli, are immunosuppressive proteins and induce pronounced IL-10 production in vitro and in vivo.. PLIF serum level, measured by enzyme-linked immunosorbent assay, was elevated in pregnant mice throughout gestation and declined towards delivery. Blocking of PLIF activity by vaccination of mice with C48 prior to mating inhibited pregnancy development. Passive transfer of anti-C48 immunoglobulin (Ig) starting at 3.5-12.5 days post coitum (dpc) resulted in high rate of embryo resorption. Furthermore, treatment with anti-C48 Ig resulted in placental and embryonal growth restriction. At gestation day 13.5, growth retardation was especially notable in the placentae, while at 16.5 dpc it was pronounced in the embryos. Histopathological examination revealed that experimental placentae were globally hypoplastic and the labyrinth was strikingly pale and contained less maternal blood compared with control. Immune-activated spleen cells harvested at 13.5 dpc from anti-C48 Ig-treated pregnant mice secreted in vitro increased level of Th1 cytokines (IL-2, TNF-alpha, IL-12) and decreased level of Th2 cytokines (IL-10, IL-4, IL-5, IL-6) as compared with the level of the respective cytokines secreted by spleen cells from control pregnant mice.. This study provides the first in vivo evidence that PLIF plays a major role in placentation and embryonic growth.

Topics: Animals; Animals, Newborn; Body Weight; Cells, Cultured; Concanavalin A; Contraception, Immunologic; Copulation; Cytokines; Delivery, Obstetric; Embryo Loss; Embryonic and Fetal Development; Enzyme-Linked Immunosorbent Assay; Female; Ferritins; Fetus; Immunization, Passive; Immunoglobulins; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Placenta; Placentation; Pregnancy; Pregnancy Outcome; Pregnancy Proteins; Pregnancy, Animal; Protein Structure, Tertiary; Spleen; Th1 Cells; Th2 Cells; Vaccination

Studies were performed to determine the effects of Bcell suppression on the pathogenesis of Subgroup J avian leukosis virus (ALV-J) in broiler chickens. Neonatal chickens were treated with cyclophosphamide (CY) or PBS, and then infected with ALV-J (ADOL-7501) at 2 weeks of age. CY treatment induced B cell specific immunosuppression throughout the experiment confirmed by decreased bursal weight, intact lymphocyte mitogenetic activity stimulated by Con A and increased relative subpopulation of CD3-positive cells as measured by flow cytometry. Chickens in this experiment had Mareks disease virus exposure prior to three weeks of age as determined by the presence of lymphocytic infiltration and antibody. Virus neutralizing antibody against ALV-J was first observed at 6 weeks post-infection in some of the infected chickens in the PBS group. As expected, none of the chickens from the CY group and uninfected chickens developed virus-neutralizing antibody. The viremic status was measured by real time RT-PCR using SYBR green I dye. The percentage of viremic chickens was significantly higher, and more chickens had high titered viremia, in the CY treated group. No neoplastic foci consistent with ALVJ infection were observed in any of the experimental chickens. The frequency and intensity of viral antigen expression determined by immunohistochemistry was significantly higher in tissues from CY treated birds than those of PBS treated chickens at 3 weeks post-infection. This study showed that B cell specific immunosuppression with CY treatment in chickens resulted in increase in viremia and viral antigen load in tissues.

Topics: Animals; Avian Leukosis; Avian Leukosis Virus; Benzothiazoles; Body Weight; Bursa of Fabricius; Chickens; Concanavalin A; Cyclophosphamide; Diamines; Flow Cytometry; Immunocompromised Host; Immunohistochemistry; Immunophenotyping; Immunosuppressive Agents; Lymphocyte Activation; Organic Chemicals; Poultry Diseases; Quinolines; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Spleen; Statistics, Nonparametric; Viremia

Pyridostigmine bromide (PYR) is an anticholinesterase drug indicated for the treatment of myasthenia gravis and neuromuscular blockade reversal. It acts as a reversible cholinesterase inhibitor and was used as a pretreatment for soldiers during Operation Desert Storm to protect against possible nerve gas attacks. Since that time, PYR has been implicated as a possible causative agent contributing to Gulf War Illness. PYR's mechanism of action has been well-delineated with regards to its effects on the nervous system, yet little is known regarding potential effects on immunological function. To evaluate the effects of PYR on immunological function, adult female B6C3F1 mice were gavaged daily for 14 days with PYR (0, 1, 5, 10, or 20 mg/kg/day). Immune parameters assessed were lymphoproliferation, natural killer cell activity, the SRBC-specific antibody plaque-forming cell (PFC) response, thymus and spleen weight and cellularity, and thymic and splenic CD4/CD8 lymphocyte subpopulations. Exposure to PYR did not alter splenic and thymus weight or splenic cellularity. However, 20 mg PYR/kg/day decreased thymic cellularity with decreases in both CD4+/CD8+ (20 mg/kg/day) and CD4-/CD8- (10 and 20 mg/kg/day) cell types. Functional immune assays indicated that lymphocyte proliferative responses and natural killer cell activity were normal; whereas exposure to PYR significantly decreased primary IgM antibody responses to a T-cell dependent antigen at the 1, 5, 10 and 20 mg/kg treatment levels for 14 days. This is the first study to examine the immunotoxicological effects of PYR and demonstrate that this compound selectively suppresses humoral antibody responses.

Topics: Administration, Oral; Animals; Antibody Formation; Body Weight; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Count; Concanavalin A; Cytotoxicity, Immunologic; Dexamethasone; Erythrocytes; Female; Immunity; Immunity, Cellular; Killer Cells, Natural; Lipopolysaccharides; Lymphocyte Activation; Mice; Organ Size; Polychlorinated Dibenzodioxins; Pyridostigmine Bromide; Spleen; Thymus Gland; Vaccination

The immuno-potentiating effects of the antler-shaped fruiting body of Ganoderma lucidum (Rokkaku-Reishi, RR), which has been used as a traditional supplement for human health, were investigated in mice. BALB/c mice were administered orally with RR for 3 days at a dose of 50 mg/kg or 500 mg/kg, and interferon-gamma (IFN-gamma) production by splenocytes in response to lipopolysaccharide (LPS) was examined on day 4. The oral administration of 500 mg/kg of RR resulted in a significant increase (p<0.05) in IFN-gamma production. Stimulation of splenic adherent cells from these mice with LPS also resulted in a significant increase (p<0.05) in interleukin-12 (IL-12) production compared with that from the control mice, suggesting that splenic macrophages were activated by RR administration. Furthermore, 500 mg/kg of RR administered for 14 days resulted in a significant increase (p<0.05) in IFN-gamma production by splenocytes in response to both LPS and concanavalin A (Con A). These results suggest that not only splenic macrophages but also T cells were activated by the long-term treatment with RR in vivo. On the other hand, the production of interleukin-4 (IL-4), which is known as an allergic disease-related cytokine, was not affected by the long-term treatment with RR. Our results suggest that the oral administration of RR resulted in Th1-associated immuno-potentiating activities in vivo.

Topics: Administration, Oral; Animals; Body Weight; Cells, Cultured; Concanavalin A; Female; Glucans; Immunity; Interferon-gamma; Interleukin-12; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Plant Extracts; Reishi; Spleen; Th1 Cells; Time Factors

This study addresses three questions related to the immune response of cattle to tick salivary gland extracts. Firstly, is there a difference in the inhibition of proliferation of Concanavalin A (ConA) stimulated bovine lymphocytes induced by salivary gland extracts of the N and Y strains of Boophilus microplus? Second, is there a difference in the development rate of the Y and N tick strains? Third, does the host affect the inhibitory effect of salivary gland extract on the proliferation of ConA stimulated lymphocytes from the two tick strains? Salivary gland extract of the Y strain inhibited in vitro proliferation of lymphocytes stimulated by ConA significantly more than that of the N strain, when each strain was raised on different animals. A difference in the development rate was observed between the tick strains when raised on the same animal, with female ticks of the Y strain developing faster and reaching a greater fully engorged weight than ticks of the N strain. The difference in their rate of development did not appear to contribute to a difference in inhibitory effects of the salivary gland extracts and there was no difference between the inhibitory effects of salivary gland extracts from both strains. However, when Y strain ticks were raised on different animals, there was a significant difference in the inhibition of lymphocyte proliferation between the two salivary gland extracts. Therefore, it was concluded that there is no difference between the inhibitory effects of the two tick strains and that the host has an influence on salivary gland extract composition of B. microplus and its inhibitive properties.

Topics: Animals; Body Weight; Cattle; Concanavalin A; Female; Host-Parasite Interactions; Immune Tolerance; Larva; Lymphocytes; Molecular Weight; Salivary Glands; Salivary Proteins and Peptides; Ticks

Impaired immune function linked to obesity has been shown in both human and animal studies. The purpose of this work was to evaluate the effects of a 4-week energy restriction (50% of total energy intake) on immune function in previously diet-induced (cafeteria) overweight rats. Flow cytometric analysis revealed that the number of spleen T helper cells were significantly (P < 0.05) elevated in control and overweight energy-restricted rats as compared with groups fed ad libitum groups. The proliferative response of splenocytes to phytohaemaglutinin and concanavalin A from overweight rats after energy restriction was significantly (P < 0.05) higher compared to overweight nonrestricted rats. The cytotoxic activity of natural killer cells tended to be lower in overweight rats compared to controls. Finally, control rats under the dietary deprivation period presented higher levels of uncoupling protein 2 mRNA and lower levels of leptin receptor mRNA compared with the reference control group. These results suggest that energy restriction is able to restore, at least in part, the impaired immune response commonly observed in overweight animals.

Topics: Animals; Blood Glucose; Body Weight; Cell Division; Concanavalin A; Cytotoxicity, Immunologic; Diet, Reducing; Energy Intake; Flow Cytometry; Immunity; Ion Channels; Killer Cells, Natural; Male; Membrane Transport Proteins; Mitochondrial Proteins; Obesity; Phytohemagglutinins; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger; Spleen; T-Lymphocytes, Helper-Inducer; Triglycerides; Uncoupling Protein 2

In the current study, we have investigated the bioeffects of repeated exposure to low-frequency (50 Hz) high-intensity (20 mT; 200 G) electromagnetic field (EMF) on some immune parameters in mice. The animals were exposed to EMF daily for 30 min three times per week for 2 weeks. We also studied the possible immunomodulatory effects of two anti-radical substances known to have non-specific immunostimulant effects namely, L-carnitine (200 mg/kg body weight i.p.) and Q10 (200 mg/kg body weight, p.o.). Both drugs were given 1 h prior to each EMF exposure. Immune endpoints included total body weight, spleen/body weight ratio, splenocytes viability, total and differential white blood cell (WBCs; lymphocytes, monocytes, neutrophils) counts, as well as the lymphocyte proliferation induced by the mitogens; phytohaemagglutinin (PHA), concanavalin-A (Con-A) and lipoploysaccharide (LPS). Magnetic field decreased splenocyte viability, WBCs count, as well as mitogens-induced lymphocyte proliferation. L-carnitine, but not Q10 could ameliorate the adverse effects of EMF on the vast majority of the immune parameters tested, suggesting a possible immunoprotective role of L-carnitine under the current experimental conditions.

Topics: Animals; Antioxidants; Body Weight; Carnitine; Cell Survival; Coenzymes; Concanavalin A; Electromagnetic Fields; Lipopolysaccharides; Lymphocytes; Male; Mice; Mitogens; Monocytes; Neutrophils; Phytohemagglutinins; Radiation-Protective Agents; Spleen; Stimulation, Chemical; Time Factors; Ubiquinone

We describe changes in the immune system of the newly established mutant line, ataxia and male sterility (AMS) mouse, and that the putative ams mutation is independent of lpr but seemed to affect lymphoproliferation in its mother strain, MRL/lpr. The mean weights of the spleen and lymph nodes of ams-lpr double-homozygous mouse were reduced compared with lpr single-homozygous mouse. Comparison between ams single-homozygous and control mice revealed 45-50% reduction of the spleen weight in the former for which reduction of the number of nucleated cells contributed greatly. In the lymphocyte/monocyte fraction of the spleen, there were significant changes in the proportion of lymphocyte subpopulations, with a reduction of B cells, an increase in CD4 and CD8 T cells, and a decrease in the CD4 : CD8 ratio. In vitro response of splenocytes to concanavalin A showed inconspicuous dose- and time-dependent responses in ams homozygous spleen, suggesting functional alteration of the immunological response. Our results indicate that ams mutation affects the immune system in addition to its two other major effects on the central nervous system and male reproductive system.

Topics: Animals; Ataxia; Autoimmunity; Body Weight; Concanavalin A; Dose-Response Relationship, Drug; Female; Genetic Linkage; Infertility, Male; Lymphocyte Subsets; Male; Mice; Mice, Inbred MRL lpr; Mice, Neurologic Mutants; Organ Size; Spleen

Animal and human studies have shown that greatly increasing the amount of fish oil [rich in long-chain (n-3) PUFA] in the diet can decrease lymphocyte functions. The effects of a more modest provision of long-chain (n-3) PUFA and whether eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) have the same effects as one another are unclear. Whether the position of 20:5 or 22:6 in dietary triacylglycerols (TAG) influences their incorporation into immune cells and their subsequent functional effects is not known. In this study, male weanling rats were fed for 6 wk one of 9 diets that contained 178 g lipid/kg and that differed in the type of (n-3) PUFA and in the position of these in dietary TAG. The control diet contained 4.4 g alpha-linolenic acid (18:3)/100 g total fatty acids. In the other diets, 20:5 or 22:6 replaced a portion (50 or 100%) of 18:3, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant dose-dependent increases in the proportion of 20:5 or 22:6 in spleen mononuclear cell phospholipids when 20:5 or 22:6 was fed. These increases were at the expense of arachidonic acid and were largely independent of the position of 20:5 or 22:6 in dietary TAG. Spleen lymphocyte proliferation increased dose dependently when 20:5 was fed in the sn-1(3) position of dietary TAG. There were no significant differences in interleukin-2, interferon-gamma or interleukin-10 production among spleen cells from rats fed the different diets. Prostaglandin E(2) production by spleen mononuclear cells was decreased by inclusion of either 20:5 or 22:6 in the diet in the sn-1(3) position. Thus, incorporation of 20:5 or 22:6 into spleen mononuclear cell phospholipids is not influenced by the position in dietary TAG. However, the pattern of incorporation may be influenced, and there are some differential functional effects of the position of long-chain (n-3) PUFA in dietary TAG. A moderate increase in the intake of 20:5 at the sn-1(3) position of dietary TAG increases lymphocyte proliferation.

Topics: Animals; Body Weight; Cell Division; Cells, Cultured; Concanavalin A; Cytokines; Diet; Eicosapentaenoic Acid; Fatty Acids; Leukocytes, Mononuclear; Lymphocytes; Lymphoid Tissue; Male; Molecular Structure; Organ Size; Phospholipids; Rats; Rats, Inbred Lew; Spleen; Triglycerides

Leptin-deficient ob/ob mice are protected from Con A-induced hepatitis. However, it is unclear whether leptin deficiency or obesity itself is responsible for this protection. To address this question, wild-type (WT) obese mice with high serum leptin levels were generated by injection of gold thioglucose (WT GTG). Both Con A-injected WT and WT GTG mice developed hepatitis, whereas no hepatic damage was observed in ob/ob mice. Moreover, TNF-alpha and IFN-gamma levels as well as expression of the activation marker CD69 were elevated in liver mononuclear cells of WT and WT GTG mice, but not in ob/ob mice following administration of Con A. The liver of WT and WT GTG mice had the same percentage of NK T cells, a lymphocyte population involved in Con A-induced hepatitis. This population decreased equally in both WT and WT GTG mice after Con A injection. In contrast, the liver of ob/ob mice contained 50% less NK T cells compared to WT and WT GTG mice. Furthermore, no decrease in NK T cells was observed in Con A-injected ob/ob mice. We conclude that leptin-deficiency, not obesity, is responsible for protection from Con A-induced hepatitis.

Topics: Animals; Aurothioglucose; Body Weight; Chemical and Drug Induced Liver Injury; Concanavalin A; Female; Interferon-gamma; Killer Cells, Natural; Leptin; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; T-Lymphocyte Subsets; Tumor Necrosis Factor-alpha

Anorexia that develops in chronic hepatitis is associated with cytokine expression in the brain. Treatment of mice with concanavalin A (12.5 mg/kg, i.v.) elevated the plasma alanine aminotransferase activity at 8.5 h after treatment. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta mRNA expression was induced at 6 and 24 h after concanavalin A treatment in both the liver and brain. Treatment of mice with concanavalin A reduced the body weight at 24 h after treatment and this decreased body weight was accompanied by a decreased food intake. Glycyrrhizin (200 mg/kg, i.p.) inhibited the concanavalin A-induced elevation of plasma alanine aminotransferase activity, however, it did not inhibit the concanavalin A-induced decreased body weight. The present results indicate that treatment of mice with concanavalin A caused the development of anorexia and that this anorexia might develop independently of the induction of hepatitis.

Topics: Alanine Transaminase; Animals; Anorexia; Body Weight; Brain; Chemical and Drug Induced Liver Injury; Concanavalin A; Disease Models, Animal; Eating; Female; Glycyrrhizic Acid; Hepatitis, Animal; Interleukin-1; Liver; Mice; Mice, Inbred BALB C; RNA, Messenger; Tumor Necrosis Factor-alpha

The effects of carbofuran (2,3-dihydro-2,2-dimethyl-7-benzo-furanol N-methylcarbamate) on the functions of T cells in splenocytes and peritoneal macrophages were examined in view of T-cell-mediated immune response (CMIR) in male C57BL/6 mice. Intraperitoneal administration of carbofuran (0.075, 0.15 and 0.3 mg/kg body weight) resulted in significant suppression of delayed type hypersensitivity (DTH), indicating that it caused the suppression of CMIR. Carbofuran decreased Concanavalin A (Con A)- and alloantigen-induced proliferation, and interleukin (IL)-2 production of splenocytes. In vitro addition of rIL-2 could not completely restore the suppressed T-cell proliferation, and IL-2-induced proliferation of Con A-activated splenocytes was also suppressed, which implied that carbofuran caused defects in IL-2 production and responsiveness of splenocytes to IL-2, leading to the suppression of T-cell proliferation. Con A-induced production of interferon-gamma (IFN-gamma) was significantly suppressed by carbofuran, while that of IL-4 was not affected. The production of transforming growth factor-beta from splenocytes was also significantly inhibited by carbofuran. Judging from these results, carbofuran might directly suppress the cytokine production in T helper 1 (Th1) cells. In addition, IFN-gamma-induced production of nitric oxide (NO) in macrophages was also inhibited by carbofuran, which might be one of the important mechanisms of carbofuran-induced CMIR suppression in mice. Collectively, the present study suggests that carbofuran might suppress CMIR through the suppression of T-cell responsiveness, IFN-gamma production in Th1 cells, and NO generation in macrophages.

Topics: Animals; Body Weight; Carbofuran; Cell Division; Concanavalin A; Cytokines; Disease Models, Animal; Drug Interactions; Hypersensitivity, Delayed; Immunity, Cellular; Insecticides; Interferon-gamma; Interleukin-2; Interleukin-4; Isoantigens; Macrophages; Mice; Mice, Inbred C57BL; Nitric Oxide; Organ Size; Spleen; T-Lymphocytes; Transforming Growth Factor beta

Treatment of mice with concanavalin A (Con A) (12.5 mg/kg, i.v.) decreased the body weight at 24 h. This Con A-induced body weight decrease was accompanied by reduction in food and water intake. Zaltoprofen is a non-steroidal anti-inflammatory drug. The administration of Zaltoprofen (10 mg/kg) at 8 h after Con A treatment was found to inhibit the Con A-induced reduction in body weight. The food intake in mice treated with Con A plus Zaltoprofen (10 mg/kg) was four times greater than that in mice treated with only Con A. The present results showed inhibition of the Con A-induced body weight loss by Zaltoprofen and suggested its possible effectiveness for the treatment of "sickness behavior".

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzopyrans; Body Weight; Concanavalin A; Dose-Response Relationship, Drug; Drinking; Eating; Female; Mice; Mice, Inbred BALB C; Propionates; Weight Loss

The seasonal effects of photoperiod on reproduction are mediated by melatonin, and it is hypothesized that increased immune function in short days is due to the increase in the duration of nightly melatonin secretion. Melatonin can act both directly and indirectly on target tissue within the immune system. The present study sought to tease apart the direct and indirect effects of melatonin on one aspect of immune function by examining the influence of in vitro melatonin on splenocyte proliferation in female prairie voles held in long (LD 16:8) or short (LD 8:16) days. Splenocyte proliferation in response to the T-cell mitogen concanavalin A was enhanced by the addition of melatonin in vitro, as compared to cultures receiving no melatonin. Body mass increased in short-day housed prairie voles, indicating that the animals were responsive to photoperiod. However, photoperiod did not affect splenocyte proliferation in the present study. These results support the hypothesis that melatonin exerts a direct effect on splenocyte proliferation, potentially via high-affinity melatonin receptors localized on splenocytes. The findings also indicate that, irrespective of photoperiod, melatonin exerts direct effects on splenocytes to enhance immune function.

Topics: Animals; Arvicolinae; Body Weight; Cell Division; Concanavalin A; Female; Immunity, Cellular; Lymphocyte Activation; Melatonin; Photoperiod; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Receptors, Melatonin; Seasons; Spleen; T-Lymphocytes

The lymphoproliferative response and T lymphocyte subsets were evaluated at different stages of carcinogenesis in male Wistar rats sequentially initiated with N-diethylnitrosamine (DEN), N-butyl-N-4(hydroxybutyl)nitrosamine (BBN), N-methyl-N-nitrosourea (MNU), dihydroxy-di-N-propylnitrosamine (DHPN) and N, N'-dimethylhydrazine (DMH) (DMBDD initiation). One group was evaluated at the 4th week and other initiated group at the 30th week. Two initiated groups were also exposed through diet to 2-acetylaminofluorene (2-AAF) or phenobarbital (PB), from the 6th until the 30th week. Two groups received only 2-AAF or PB until the 30th week. Five groups were studied to evaluate the effects of each initiator. The lymphoproliferative response was induced in vitro by concanavalin A and the percentage of T lymphocyte subsets was determined by flow cytometry. All groups submitted to initiation only, initiation plus promotion, or promotion only, developed significantly more preneoplastic lesions than the untreated control group. The main target organs for tumor development were the liver, colon, urinary bladder, kidneys and Zymbal glands, mainly in the group treated with DMBDD+2-AAF. There were no alterations of the lymphoproliferative response and of the T lymphocyte subsets percentage in the DMBDD-treated group at the 4th and 30th weeks. At the 30th week, the T lymphocyte subsets percentage was also not affected in the initiated groups after treatments with 2-AAF or PB. The lymphoproliferative response, however, was decreased in the DMBDD+2-AAF group and in the groups treated only with 2-AAF or PB. The present results indicate that the initiating chemicals used in the DMBDD initiation protocol do not exert any influence on the immune system. The alteration of lymphoproliferative response induced at the advanced stage of carcinogenesis without alteration of T lymphocyte subsets may indicate that the influence of 2-AAF and PB on the immune system is functional and not toxic.

Topics: 1,2-Dimethylhydrazine; 2-Acetylaminofluorene; Alkylating Agents; Animals; Body Weight; Butylhydroxybutylnitrosamine; Carcinogenicity Tests; Carcinogens; Concanavalin A; Diethylnitrosamine; Flow Cytometry; Male; Methylnitrosourea; Neoplasms, Experimental; Nitrosamines; Phenobarbital; Rats; Rats, Wistar; Spleen; T-Lymphocyte Subsets; Tissue Distribution

Although the early identification of patients with suboptimal nutritional status can allow the implementation of nutritional intervention to enhance the ability of the body to fight infection and disease, currently no definitive test of nutritional status exists. Therefore, this study was conducted to identify possible functional indicators of acute nutritional deprivation. The effects of total nutritional deprivation and subsequent refeeding on lymphocyte functions and subpopulations were examined in 23 healthy cats. Peripheral blood samples were analyzed at various times during food deprivation and refeeding periods. During the food deprivation period, decreases were observed in leukocyte number (P: < 0.05), lymphocyte number (P: < 0.05), percentage of CD4(+) cells [before stimulation with concanavalin-A (Con-A); P: < 0.05] and the CD4/CD8 ratio (before stimulation with Con-A; P: < 0.01) compared with d 0. Increases were observed in the percentage of CD8(+) cells [before (P: < 0.05) and after (P: < 0.01) stimulation with Con-A] and in intracellular calcium (P: < 0.01) during acute starvation. During the refeeding period, increases were observed in the percentage of CD4(+) cells (before and after stimulation with Con-A; P: < 0.01), the percentage of CD8(+) cells (before stimulation with Con-A; P: < 0.05) and lymphocyte number (P: < 0.05) compared with d 7. Lymphocyte proliferative capacity tended to decrease (P: = 0.07) during starvation and increased (P: < 0.01) during the refeeding period. These findings suggest that a 7-d starvation period had immunosuppressive effects on cats and that these effects were not completely normalized during 7 d of refeeding. CD4(+)/CD8(+) subset alterations and CD4/CD8 ratio in conjunction with lymphocyte proliferation may be useful as indices of nutritional status.

Topics: Animals; Body Weight; Calcium; Cats; CD4 Lymphocyte Count; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; Concanavalin A; Food; Leukocyte Count; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Subsets; Models, Animal; Serum Albumin; Starvation

We investigated the effects of iron deficiency anemia, iron repletion, and iron chelation by deferoxamine on protein kinase C (PKC) activity, an enzyme that plays a crucial role on T lymphocyte proliferation. The study involved 23 control (C), 18 pairfed (PF), and 24 iron deficient (ID) mice or ID mice that were repleted for 3 (n = 14), 7 (n = 17), or 14 (n = 14) days. The low iron (0.09 mmol iron/kg) and iron-supplemented (0.9 mmol iron/kg) diets were fed to mice for 53 days. Mean hemoglobin, hematocrit, and liver iron stores of ID mice were one third of those of C mice. Lymphocyte proliferation was reduced (P < 0.05) in spleen and purified T cells in ID but not PF mice. In concanavalin A, phytohemagglutinin, and anti-CD3 antibody-treated and untreated cells that were incubated in serum-free and serum-containing medium, PKC activity was significantly (P < 0.05) reduced in ID but not PF mice and returned to normal before correction of anemia. In mitogen-treated cells, while the ratios of membrane-bound to cytosol activity increased nearly seven-fold (from 0.4-0.63 in resting cells to 1.43-7.23) in spleen cells from C, PF, and repleted mice and 11-fold in T cells (P < 0.005), they remained below 1 in ID mice suggesting reduced translocation. In vitro iron chelation by deferoxamine for 120 min prior to cell activation reduced (P < 0.05) PKC activity by 46-60% in C and PF and 28-53% in ID mice. The data suggest that: 1) it is iron-deficiency but not anemia or differences in the proportion of immunocompetent T cells that reduced PKC activity in cells from ID mice; 2) reduced PKC translocation may play an important role on altered lymphocyte proliferation and associated functions in iron-deficient individuals.

Topics: Anemia, Iron-Deficiency; Animals; Body Weight; CD3 Complex; Cell Division; Cell Membrane; Cells, Cultured; Chelating Agents; Concanavalin A; Culture Media, Serum-Free; Cytosol; Deferoxamine; Female; Hemoglobins; Iron; Iron, Dietary; Liver; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mitogens; Phytohemagglutinins; Protein Kinase C; Spleen; T-Lymphocytes; Time Factors

Mitogenic responses were examined for purified peripheral blood mononuclear cells (PBMC) and whole blood from individuals in a line (F) of turkeys selected for increased 16-wk BW and its corresponding randombred control (RBC2). The PBMC were isolated by centrifugation over Histopaque-1077 density gradient and tested for mitogenic responses to concanavalin A (Con A; 25 microg/mL) and phytohemagglutinin (PHA)-M; 100 microg/mL). For the whole blood assay, 6-wk-old poults from both lines were injected with inactivated Pasteurella multocida. Heparinized blood samples were collected prior to injection (0 d) and at 2, 4, 7, and 14 d postinjection. The diluted whole blood was then tested for the mitogenic responses to Con A (25 microg/mL) and PHA-M (25 microg/mL). The cultures were then pulsed with 3H-thymidine, and incorporation was measured using a liquid scintillation counter. There was a line difference in the mitogenic responses to Con A for PBMC and whole blood assays, but no line difference was observed in the response to PHA-M for both assays. For the purified PBMC assay, the F line had a lower response than its randombred control line (P < or = 0.05) to Con A expressed as either cpm or a stimulation index (SI; ratio of cpm for stimulated cells to the cpm for unstimulated cells). For the whole blood assay, the F line had generally lower SI values in the responses to Con A than the RBC2 line, with differences being significant at 0 and 2 d postinjection (P < or = 0.01) and at 14 d postinjection (P < or = 0.05). Genetic selection for increased BW might have affected the lymphoblastogenic potential of Line F that could affect disease resistance.

Topics: Animals; Body Weight; Cell Division; Cells, Cultured; Concanavalin A; Female; Immunity, Cellular; Immunity, Innate; Leukocytes, Mononuclear; Male; Mitogens; Pasteurella multocida; Phytohemagglutinins; Selection, Genetic; Turkeys

An experiment was conducted to investigate the effects of the lectin, Concanavalin A (Con A), contained in raw Jack bean (JB) (Canavalia ensiformis, L.) seeds on the immunological response of broilers. A maize-soybean meal basal diet was prepared to which either 2.5, 5, or 10% of ground raw Jack bean (RJB) seeds was added. The RJB seeds contained 24 g Con A/kg on a dry matter basis, as measured by rocket immunoelectrophoresis. Similar diets were prepared by using the same levels of JB after toasting at 190 C for 16 min. In addition, the basal diet was pair-fed to groups of chicks at the level of feed intake of chicks fed the 10% RJB diet. Each diet was fed to six groups of six chicks for 6 wk. At 5 wk, 15 of chicks from each diet were immunized against Brucella abortus (BA) and the anti-BA antibody titers were determined 1 wk later by ELISA. Antibody production against Con A was also measured by the same method. Binding of Con A to intestinal villi and subsequent endocytosis were confirmed by microscopic examination using a specific peroxidase-antiperoxidase-staining technique. Performance was recorded weekly. Feed intake and weight gain were reduced (P < 0.05) only by the diet containing 10% RJB, indicating that broiler chicks can tolerate daily intakes of 100 mg of Con A over 6 wk without affecting growth. Toasted JB diets supported adequate chick performance. The antibody response to BA did not differ with dietary treatment. Serum from chicks fed raw JB also contained antibodies against Con A. The bursa of Fabricius, thymus, spleen, and pancreas dry weights, as a percentage of dry body weight, were not affected by the experimental diets. The data indicated that Con A binds to the cells of the gastrointestinal tract, passes into the general circulation and, eventually, elicits an immunological response without affecting the production of antibodies to BA.

Topics: Animal Nutritional Physiological Phenomena; Animals; Antibodies, Bacterial; Body Weight; Brucella abortus; Brucella Vaccine; Chickens; Cohort Studies; Concanavalin A; Duodenum; Eating; Fabaceae; Immune Sera; Immunoglobulin G; Liver; Male; Microvilli; Organ Size; Plant Lectins; Plants, Medicinal; Rabbits; Random Allocation; Seeds

Biotin deficiency is known to affect immune function in both humans and experimental animals. In this study, we determined the effect of biotin deficiency on 4-wk-old Balb/cAnN mice during 20 wk of experimentation. The growth rate of mice slowed significantly during the first 6 wk of consumption of a diet designed to induce biotin deficiency; thereafter, from weeks 7 to 20 there was progressive weight loss in the mice receiving the biotin-deficient diet. In the livers of biotin-deficient mice, the specific activities of two biotin-dependent enzymes--pyruvate carboxylase and propionyl-CoA carboxylase--decreased by as much as 75% and 80%, respectively, and in spleen lymphocytes the specific activities of these two enzymes decreased by 63% and 75%, respectively. With respect to the effects of biotin deficiency on the immune system, we observed statistically significant changes in both the absolute number of spleen cells and in the proportions of spleen cells carrying different phenotypic markers: after 16 wk the percentage of cells expressing surface immunoglobulin (sIg) decreased from 47% (control and supplemented) to 27% (deficient) and CD3+ cells increased from 42% (control and supplemented) to 54% (deficient). The mitogen-induced proliferation of spleen cells from deficient mice was lower than that of spleen cells from the control mice. These findings suggest that biotin could have an important role in lymphocyte maturation and responsiveness to stimulation, and consequently in the capacity of the immune system to respond to an antigenic challenge.

Topics: Animals; Biotin; Body Weight; Carboxy-Lyases; Cell Division; Concanavalin A; Deficiency Diseases; Lymphocyte Subsets; Lymphocytes; Male; Methylmalonyl-CoA Decarboxylase; Mice; Mice, Inbred BALB C; Pyruvate Carboxylase; Spleen

Poly I:C, an inducer of IFN-alpha and other cytokines, has been used to study the development of diabetes in both the BioBreeding (BB) diabetes prone rat and non-obese diabetic (NOD) mouse animal models of insulin-dependent diabetes mellitus (IDDM). Surprisingly, poly I:C accelerates the disease in the BB rat while inhibiting it in the NOD mouse. Since cytokines can have dose related opposing effects on immune responses, we hypothesized that the paradoxical effect of polyinosinic polycytidylic acid (poly I:C) on diabetes in the two animal models is dose related. Accordingly, we compared the incidence of diabetes and degree of insulitis in diabetes prone BB rats administered saline and poly I:C at doses (0.05 microg/g body weight and 0.1 microg/g body weight) up to 100-fold lower than doses (poly-5 microg/g) previously found to accelerate diabetes. In addition, the non-specific suppressor activity of mononuclear splenocytes from BB rats administered low dose (poly-0.05 microg/g body weight), high dose (poly-5 microg/g body weight), and saline were compared. The development of diabetes was inhibited in rats treated with each dose of poly I:C. The degree of insulitis in poly-I:C treated animals was also less severe. The total white blood cell count and proportion of RT6+ T-cells and each T-cell subset were unaltered by poly I:C. When compared to splenocytes of control animals, splenocytes from poly I:C (0.05 microg/g body weight) treated rats suppressed responder cell proliferation to concanavalin A and alloantigen. However, spleen cells from high dose poly-I:C did not suppress responder cell proliferation to alloantigen. In adoptive transfer studies, the administration of spleen cells from poly-0.05 treated rats decreased the development of diabetes in recipient BB rats. In vitro studies also demonstrated that poly-I:C inhibits the proliferative response of BB rat spleen cells to concanavalin A. The administration of poly-0.05, but not poly-5.0, decreased TNF-alpha mRNA and IL-10 mRNA content in spleen cells. We conclude that poly I:C, at a dose 100 times lower than that required to accelerate diabetes prevents the development of diabetes in BB rates by interfering with the development of insulitis. The induction of suppressor cell activity induced by low dose poly-I:C in vivo and the inhibition of T-cell responses by poly-I:C in vitro suggests that the diabetes sparing activity of poly I:C is mediated by augmented immunoregulatory cell activity. Further st

Topics: Animals; Body Weight; Concanavalin A; Cytokines; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Flow Cytometry; Gene Expression; Histocompatibility Antigens Class I; Interferon Inducers; Islets of Langerhans; Leukocyte Count; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Phenotype; Poly I-C; Rats; Rats, Inbred BB; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory

Selection of poultry for fast growth rate is often accompanied by a reduction in specific immune responses or increased disease susceptibility. In this study, 17-wk-old male turkeys from each of four closed genetic lines, a randombred control (RBC) line and its subline (F) selected for increased 16-wk BW, and another RBC and its subline (E) selected for increased egg production, were tested for in vivo response to toe web inoculation with phytohemagglutinin-P (PHA-P), in vitro response of lymphocytes in whole blood to PHA-P and concanavalin A (Con A), hemolytic complement activity, differential white blood cell counts, hematology, and serum chemistry values. Fifteen male turkeys from each of two commercial lines, Com A and Com B, were also tested. The large-bodied F line birds had a lower toe web response to PHA-P, lower lymphocyte counts, and lower relative spleen weights than their smaller parent line. Body weights, total erythrocyte counts, blood urea nitrogen (BUN) levels, and in vitro mitogenic response to PHA-P and Con A were higher in the F line birds. Line E had lower hemolytic complement levels, lower relative spleen and relative bursal weights, and a higher in vitro mitogenic response to PHA-P than its parent line. The Com B line had a lower toe web response to PHA-P, and lower serum levels of gamma-glutamyltransferase and bilirubin than Com A. Line Com B had higher total RBC counts and higher levels of alanine aminotransferase (ALT) than Com A. These results support the concept that some changes in the cell-mediated immune response, as well as other physiological changes that may potentially affect immune response, appear to accompany selection for faster growth.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Blood Urea Nitrogen; Body Weight; Breeding; Cells, Cultured; Complement System Proteins; Concanavalin A; Eggs; Erythrocyte Count; Female; gamma-Glutamyltransferase; Growth; Hemolysis; Hypersensitivity; Leukocyte Count; Lymphocyte Activation; Lymphocyte Count; Lymphocytes; Male; Organ Size; Oviposition; Phytohemagglutinins; Spleen; Turkeys

Three experiments were conducted to determine the effects of supplementing practical diets of male turkeys with dl-alpha-tocopheryl acetate (TA). In Experiment 1, a factorial arrangement of dietary treatments [0, 12, 50, 150, and 300 IU TA/kg with 0 or 300 mg ascorbic acid (AA)/kg] was used. These 10 treatments were fed to poults from 1 to 41 d of age. From 41 to 118 d of age, the AA treatments were discontinued, and the 300 IU TA treatment groups were changed to 12 IU TA/kg. Neither TA nor AA treatments affected 41-d BW, feed to gain ratio (FE), or livability. No effects of dietary TA concentrations on turkey performance were observed through 118 d of age alpha-Tocopherol (TOC) concentrations of plasmas and livers were increased by increments of dietary TA, with substantial liver storage when toms were fed 150 IU TA/kg from 1 to 118 d. Supplementing diets with 0, 25, 50, 75, or 100 IU TA/ kg in Experiments 2 and 3 had no effect on performance of toms through 119 and 105 d, respectively. alpha-Tocopherol concentrations of plasma and red blood cells (RBC) increased linearly with increments of dietary TA. The same was true for livers in Experiment 2. Susceptibility of RBC to hemolysis induced by 400 microM t-butyl hydroperoxide (TBH) in Experiment 2 decreased with increasing dietary TA, and these decreases corresponded to increases in TOC concentration of RBC. However, the relationships between hemolysis and dietary TA or RBC TOC were inconsistent in Experiment 3 and varied according to concentration of TBH (200, 300, or 400 microM) and age of the toms. At 105 d of age, RBC of toms fed no supplemental TA were resistant to hemolysis, irrespective of dietary TA and TBH concentration. In Experiment 3, there were no indications of dietary TA effects on plasma peroxide concentration or activity of plasma creatine kinase. A positive relationship between dietary TA and blastogenic responses of blood lymphocytes was observed with concanavalin A when toms were at 44 d but not at 23 or 86 d of age. The overall data indicate that corn-soybean meal diets containing from 6 to 20 IU TOC/kg, but no supplemental TA supported satisfactory performance and well-being of male turkeys from 1 d of age to market ages when the turkeys were free of disease, as was true in the research reported here.

Topics: Aging; Analysis of Variance; Animals; Body Weight; Concanavalin A; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Erythrocyte Count; Glycine max; Lipopolysaccharides; Liver; Lymphocyte Activation; Male; Peroxides; Plant Lectins; Regression Analysis; tert-Butylhydroperoxide; Turkeys; Vitamin E; Zea mays

The present experiments were conducted to investigate influences of dietary methionine and cysteine on metabolic responses to immunological stress induced by Escherichia coli lipopolysaccharide (LPS) injection, and concanavalin A (Con A)-induced mononuclear cell (MNC) proliferation in male broiler chickens. In Expt 1, chicks (12 d of age) were fed on a S amino acid (SAA)-deficient diet (5.6 g SAA/kg diet) or on three kinds of SAA-sufficient diet (9.3 g SAA/kg diet; low-, medium- and high-cysteine diets) which contained 2.8, 4.65 and 6.5 g cysteine/kg diet, respectively. Plasma alpha-1 acid glycoprotein (AGP) concentration and interleukin (IL)-1-like activity in chicks fed on the SAA-deficient diet were lower following a single injection of LPS than those in chicks fed on the SAA-sufficient diets. At 16 h after LPS injection, plasma Fe and Zn concentrations and body weight were reduced, but AGP concentration and IL-1-like activity in plasma were significantly increased. These changes in body weight, plasma Zn and Fe concentrations following injection of LPS were not affected by dietary methionine: cysteine ratios. Plasma AGP concentration and IL-1-like activity in chicks fed on the high-cysteine diet were, however, greater than those in chicks fed on the other diets following a single injection of LPS. In Expt 2, chicks (7 d of age) were fed on the SAA-sufficient diets as in Expt 1 for 10 d. MNC proliferation in spleen induced by Con A in chicks fed on the high-cysteine diet was greater than that in chicks fed on the low- or medium-cysteine diet. The results suggest that dietary cysteine has an impact on the immune and inflammatory responses.

Topics: Acute-Phase Reaction; Amino Acids; Animals; Body Weight; Chickens; Concanavalin A; Cysteine; Diet; Escherichia coli; Interleukin-1; Iron; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Methionine; Mitogens; Random Allocation; Spleen; Thymus Gland; Zinc

The action of deltamethrin, a potent type II synthetic pyrethroid insecticide, on the thymus of the Balb/c mouse was studied in vivo and in vitro. We found that deltamethrin produced atrophy in the thymus in a dose- and time-dependent fashion. The lowest effective dose was found to be 6 mg/kg, 24 hr after a single intraperitoneal treatment. Treated animals did not recover during the time-course of the experiment (365 days after treatment); however, deltamethrin did not affect the body weight of the treated animals during the course of the study. To determine if deltamethrin-induced [Ca2+]i signaling could lead to thymic atrophy via programmed cell death, mice were treated with 25 mg deltamethrin/kg for 24 hr or the isolated thymocyte suspension was treated with 50 microM deltamethrin. A significant stimulation of inositol 1,4,5-triphosphate (IP3) and inositol 1,4-diphosphate (IP2) production was found after 24 hr of deltamethrin-1R (active isomer) treatment. An inactive stereoisomer of deltamethrin (i.e. 1S) did not cause a significant rise in the production of 1P3 and 1P2. In addition, deltamethrin-1R induced a transient increase of [Ca2+]i mobilization in the thymocyte suspension after 10 min of in vitro treatment, and substantially reduced the rate of calcium-calmodulin (Ca/CaM)-dependent protein dephosphorylation in in vivo treated animals (25 mg deltamethrin/kg for 24 hr). The in vivo effects of deltamethrin treatment demonstrated induction of DNA fragmentation and cell death in thymocytes. Moreover, using a histochemical approach, it was evident that deltamethrin at 25 mg/kg was able to produce cell death in the thymus of treated animals 72 hr after treatment. In the present work, we found that cell death was apoptotic in nature as noted first by the inhibition of deltamethrin-induced cell death by aurintricarboxylic acid, an inhibitor of apoptosis, and second, by internucleosomal DNA fragmentation, a hallmark of apoptosis, produced by deltamethrin in treated animals as well in thymocyte suspensions. In addition, the involvement of the Ca/CaM-dependent protein phosphorylation-dephosphorylation cascade in the induction of apoptosis by deltamethrin was supported by the protective role of the calmodulin inhibitor trifluoperazine against the apoptotic effect of deltamethrin on thymocyte suspension. Our results suggest that deltamethrin induced thymus atrophy and altered the Ca/CaM-dependent protein kinase-phosphatase cascade, which might induce programm

Topics: Animals; Apoptosis; Atrophy; Body Weight; Cell Survival; Cells, Cultured; Concanavalin A; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Insecticides; Kinetics; Male; Mice; Mice, Inbred BALB C; Nitriles; Pyrethrins; Signal Transduction; Stereoisomerism; T-Lymphocytes; Thymus Gland

Murine retrovirus infection causes an aberrant stimulation of several subsets of T helper 2 cells identified by their T cell receptors (TCR). C57BL/6 mice were treated with synthetic peptides based upon different human TCR V beta CDR1 sequences following experimental infection with the murine retrovirus. Previous studies established that retrovirally infected mice produced autoantibodies to certain of these peptides, and their administration after infection diminished many of the cytokine abnormalities induced by the virus. This study determined whether the complete 16-mer synthetic peptides modeling the V beta CDR1/FR3 were required, and whether admixture of autoantigenic peptides synergized immune preservation. Treatment with complete TCR pep beta 3 and pep V beta 5.2 peptide alone and combined largely prevented the retrovirus-induced reduction in B and T cell proliferation and Th1 cytokine secretion while suppressing excessive production of Th2 cytokines, which are stimulated by retrovirus infection. Treatment with overlapping short peptides corresponding to the N-terminal 11-mer and C-terminal 12-mer did not significantly prevent the immune dysfunction in retrovirus-infected mice. These data suggest that immune dysfunction and abnormal cytokine production, induced by murine retrovirus infection, were largely prevented by TCR V beta CDR1 peptides, and the complete CDR1 in association with the five residues from FR2 was required.

Topics: Amino Acid Sequence; Animals; B-Lymphocytes; Body Weight; Cell Division; Cells, Cultured; Concanavalin A; Cytokines; Female; Leukemia Virus, Murine; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mitogens; Molecular Sequence Data; Murine Acquired Immunodeficiency Syndrome; Peptides; Receptors, Antigen, T-Cell, alpha-beta; Spleen; T-Lymphocytes; Vaccination

Concanavalin A (Con A), a plant lectin, was injected iv into pregnant rats as a single dose of 5, 10 or 20 mg/kg on gestational day (GD) 8, to investigate developmental toxicity in foetuses at term and to examine histologically embryos between GD 10 and 12. There were high incidences of various malformations in the 10 and 20 mg/kg groups: externally, craniofacial dysplasia and closure defects of the ventral body wall; internally, anophthalmia and cardiovascular malformations; and in the skeleton, anomalies of the anterior region of the vertebrae and ribs. Histological examination revealed that neural crest cells (NCC) in the control embryos appeared to be streaming from the neural crest towards the ventral region on GD 10, 11 and 12, and reached the region of the branchial arches on GD 12. By contrast, those in the Con A-treated embryos were aggregated near the dorsal region on GD 10 and 11, and had not reached the destination even on GD 12. These findings suggest that pathogenesis of developmental toxicity of Con A in rats is associated with disturbance of NCC migration and inhibition of their pluripotentiality at the destination.

Topics: Abnormalities, Drug-Induced; Analysis of Variance; Animals; Body Weight; Bone and Bones; Brain; Cell Movement; Concanavalin A; Craniofacial Abnormalities; Embryonic and Fetal Development; Female; Gestational Age; Heart Defects, Congenital; Male; Neural Crest; Pregnancy; Rats; Rats, Sprague-Dawley

The production of a prolactin (PRL)-like substance by mitogen-stimulated immunocompetent cells has been reported previously for a number of species. The Snell dwarf mouse has a deficiency in thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) as a result of a defect in the pituitary Pit-1 promoter. Since the gene for PRL is present in the dwarf mouse pituitary but not activated it was of interest to determine whether a similar deficiency existed for splenocytes from the dwarf animal. Irradiated splenocytes from dwarfs and normal littermates were cocultured in synthetic AIM-V medium with Nb2 cells and stimulated with concanavalvin A (Con-A). The 3H thymidine incorporation into Nb2 cells in cocultures was quantitated by the addition of mouse PRL to Nb2 cells alone. Splenocytes from dwarf mice produced significantly less PRL-like activity (p < 0.02) than did splenocytes from normal animals. The administration of thyroxine (T4) to dwarf mice increased body weight (BW) gain and the number of splenocytes/g BW. The administration of recombinant bovine GH but not recombinant bPRL further increased body weight gain over T4 alone but neither pituitary hormone had any additional effect on the number of splenocytes/g BW over that noted for T4 alone. Prolactin and GH alone had no effect on splenocyte numbers/g BW. The decreased production of PRL-like activity in the dwarf mouse was not altered by either GH or PRL injection. The injection of T4 alone and in combination with pituitary hormones increased the production of PRL-like activity by dwarf splenocytes to values similar to that observed for normal animals.

Topics: Animals; Body Weight; Cells, Cultured; Concanavalin A; Drug Interactions; Female; Growth Hormone; Lymphoma; Male; Mice; Mice, Inbred C3H; Prolactin; Spleen; Stimulation, Chemical; Thyroxine; Tumor Cells, Cultured

The effect of glutamine (Gln)-supplemented diet on mitogen response decreased immediately after a treadmill exercise was examined by measuring the proliferations of peripheral blood lymphocytes (PBL) with phytohemagglutinin (PHA) and concanavalin A (ConA) in male Fisher rats. Although the plasma Gln concentration was significantly decreased in the control group immediately after a treadmill exercise (20 m/min, 60 min) compared to rested rats, plasma Gln concentration of rats fed Gln-supplemented diet for 3 weeks was significantly higher than that of control group in resting and was not significantly decreased even immediately after a treadmill exercise. In addition, proliferation of PBL with PHA or ConA and interleukin 2 (IL2) production were also significantly decreased immediately after a treadmill exercise in control group. On the contrary, their functions were almost maintained in Gln-supplemented group even immediately after a treadmill exercise. PBL from rats fed Gln-supplemented diet showed a higher response to mitogens such as PHA and ConA compared to the control group. Furthermore, their PBL showed higher incorporation of [3H]Gln compared to that of the control group irrespective of treadmill exercise. These results indicate that the preventive effect of Gln-supplemented diet on mitogen response decreased after a treadmill exercise is due to an increased response to mitogen and increased uptake of Gln as sources of fuel and nucleotides to the immune cells.

Topics: Animals; Body Weight; Concanavalin A; Eating; Exercise Test; Food, Fortified; Glutamine; Interleukin-2; Lymphocyte Activation; Male; Physical Exertion; Phytohemagglutinins; Random Allocation; Rats; Rats, Inbred F344; T-Lymphocyte Subsets; Tritium

Immune competence declines following major injury, and predisposes the trauma patient to infection. Interleukin-10 (IL-10), although an immunosuppressive cytokine, is also important in the initiation of immune responses. This study investigated alterations in IL-10 and immune function associated with polymicrobial sepsis following trauma using murine femur fracture (FFx) and cecal ligation/puncture (CLP) models. Mice were randomized to Normal, FFx, Alcohol and FFx (EtOH + FFx), CLP, FFx + CLP, and EtOH + FFx + CLP. Polymicrobial sepsis was induced by performing CLP 4 days after FFx, and animals were killed 14 days later; immune function was assessed by in vitro splenocyte cultures. Lymphocyte proliferative responses were significantly suppressed in FFx and CLP animals. Splenocyte IL-10 production was significantly reduced in FFx and CLP animals, with concurrent increases in nitrite and tumor necrosis factor release. This study documents that trauma induces alterations in the inflammatory cytokine cascade that affect the immune response to subsequent septic challenges.

Topics: Animals; Body Weight; Cell Division; Concanavalin A; Immunity, Cellular; Interleukin-10; Lipopolysaccharides; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Nitrites; Sepsis; Spleen; Thymidine; Tumor Necrosis Factor-alpha; Wounds and Injuries

The standard laboratory diet administered to sand rat (Psammomys obesus) induces the following physiological and immunological changes: hyperglycemia and hypercholesterolemia involving mainly the free fraction of cholesterol, with an elevation of high-density-lipoprotein levels and a decrease in B and T splenic lymphocyte proliferation in the presence of different mitogens PHA-P, Con A and LPS. These results demonstrate the important modification that could be induced in sand rat by the standard laboratory diet as compared with natural diet, and thus the sand rat (P. obesus) appears to be an interesting model for studies on experimental diabetes mellitus.

Topics: Animals; B-Lymphocytes; Blood Glucose; Body Weight; Cells, Cultured; Cholesterol; Concanavalin A; Diabetes Mellitus, Experimental; Diet; Disease Models, Animal; Gerbillinae; Lipopolysaccharides; Lymphocyte Activation; Mitogens; Phytohemagglutinins; Spleen; T-Lymphocytes

We investigated effects of voluntary wheel running on specific antibody responses to Keyhole Limpet Hemocyanin (KLH) and on mitogen-stimulated lymphocyte proliferation in adult male rats. Each subject was placed in a running wheel for 12 h daily during the dark portion of the light cycle for a total of 8 weeks. For experimental animals the wheels rotated freely, enabling subjects to exercise at will, while for control animals the wheels were prevented from rotating. Subjects were immunized with KLH (25 micrograms) 5 weeks into the study, and blood samples were collected intermittently from the tail for 3 weeks and later assayed for anti-KLH antibody levels. At the end of the study, subjects were sacrificed and spleens were dissected and assayed for lymphocyte proliferative responses to the mitogen Concanavalin A. Exercised rats gained less weight and had higher splenic proliferative responses than control rats; however, there were no significant group differences in anti-KLH antibody levels.

Topics: Animals; Body Weight; Concanavalin A; Hemocyanins; Immunity; Lymphocyte Activation; Male; Physical Conditioning, Animal; Rats; Spleen

Selenium (Se) is an essential nutritional factor that was shown previously by us to alter the kinetics of expression of high affinity (p55/p75) interleukin 2 receptors (IL-2R). This study shows that dietary (2 ppm for 8 weeks) or in vitro (1 x 10(-7) M) supplementation with Se (as sodium selenite) results in a significant upregulation of the expression of both the p55 and p70/75 IL-2 binding sites on the surface of concanavalin A-stimulated lymphocytes from C57BL/6J mice. This resulted in the formation of significantly higher numbers of high affinity IL-2R/cell with preservation of the normal ratio of high affinity to total IL-2 binding sites/cell. The high affinity IL-2R on cells from Se-supplemented animals functioned normally in terms of ligand binding and kinetics of IL-2 internalization, but their greater numbers/cell resulted in the internalization of significantly larger amounts of IL-2/cell. As Se supplementation results in an earlier expression of greater numbers of high affinity IL-2R, the presence of Se in the cell environment can result in an accelerated clonal expansion of activated lymphocytes.

Topics: Animals; Binding Sites; Body Weight; Cells, Cultured; Concanavalin A; Diet; Interleukin-2; Kinetics; Lymphocyte Activation; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Receptors, Interleukin-2; Selenium; Time Factors; Up-Regulation

The possible relationship between fatty acid anilides and the toxic oil syndrome (TOS) which appeared in Spain in 1981 has been debated during recent years. These anilides have been detected as anomalous compound in toxic oils analysed. After treatment with one daily dose of 50 mg/kg of oleilanilide (88.86% pure) for 5 days, animals showed a tendency towards progressive loss of body weight and a significant increase in serum concentration of immunoglobulins. The percentage of suppressor T cells in spleen diminished significantly compared with the control group. Consequently, an increase in the helper T cells/suppressor T cells was also observed. The production of IgM and IgG in culture was significantly higher than in controls and no differences were seen in IgA synthesis. The functional studies of generation of specific IgM, IgA and IgG suppressor cells at variable doses of concanavalin A (Con A) showed paradoxical behaviour of suppressor T cells generated by low doses of Con A. A similar change occurred at higher doses of Con A. These results suggest that low-dose treatment with oleilanilides induces an alteration in the immune response in Swiss mice.

Topics: Anilides; Animals; B-Lymphocytes; Body Weight; Cell Count; Cell Differentiation; Concanavalin A; Dose-Response Relationship, Immunologic; Female; Immunity, Innate; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Macrophages; Mice; Oleic Acids; Organ Size; Pokeweed Mitogens; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory

Inhibitory effects of soybean protein isolate (SPI) and soybean lectin on the intestinal absorption of nonheme iron were investigated by in vivo studies in rats. Rats fed the SPI-based diet absorbed significantly less iron than did control rats fed the casein-based diet. Supplementing the SPI diets with 8% D-galactose significantly increased the incorporation of iron into liver ferritin, although D-galactose did not significantly increase iron absorption. Heat treatment of SPI significantly increased iron absorption. Ascorbate did not enhance iron absorption in rats fed the SPI-based diet. The presence of lectin in an aqueous extract of SPI was suggested by hemagglutination activity as well as by immunoreactivity with soybean lectin antibody. Soybean lectin introduced into ligated segments of the upper small intestine of rats inhibited ferrous iron absorption. This inhibitory effect, especially in the mucosal uptake, was significantly improved by addition of N-acetyl-D-galactosamine to soybean lectin. Soybean lectin had no effect on ferric iron absorption. Our results suggest that a portion of the reduction in iron absorption in rats fed SPI may be due to lectins.

Topics: Animals; Body Weight; Concanavalin A; Dietary Proteins; Ferritins; Glycine max; Hemagglutination Tests; Intestinal Absorption; Iron; Lectins; Liver; Male; Plant Lectins; Rats; Rats, Inbred Strains

Recent studies indicate that supplemental arginine may enhance in vitro lymphocyte mitogenesis. To determine whether dietary arginine could reverse age-associated losses in immune functions, we fed purified amino acid diets to young (2-mo-old) and aged (24-mo-old) Fischer 344 rats. Rats receiving control (1.12% arginine) or supplemented (3% arginine) diets were pair fed to intakes of deficient (0% arginine) rats. Another group was fed the supplemented diet ad libitum. On d 15, responses of splenocytes to phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were lower (P less than 0.01), but interleukin-2 (IL-2) production was higher (P less than 0.05) in aged rats than in young rats. At mitogen doses producing maximal stimulation, supplemental arginine did not enhance PHA-, Con A- or PWM-stimulated lymphocyte proliferation; PWM responses at sub-maximal doses were higher in pair-fed supplemented rats than in control or ad libitum supplemented rats (P less than 0.05). Arginine supplements did not increase thymus weights or IL-2 production above controls. In another experiment, weanling rats received control and supplemented diets in amounts equal to the intake of deficient rats for an average of 37 d. Splenocytes were cultured with mitogens at various arginine levels. No diet effect was observed. Mitogenesis was maximal when media arginine approximated normal plasma levels. Our results suggest that supplemental arginine has little effect on lymphocyte proliferation or IL-2 production in healthy young and aged rats.

Topics: Aging; Alanine; Animals; Arginine; Body Weight; Citrulline; Concanavalin A; Diet; Glutamine; Interleukin-2; Lymphocyte Activation; Male; Organ Size; Ornithine; Phytohemagglutinins; Pokeweed Mitogens; Rats; Rats, Inbred F344; Spleen

The effect of the novel agent gamma-(2-aminoethylamino)-2-butyrothienone (gamma-ABT) on local and systemic changes of rats with adjuvant induced disease (AID) was investigated, gamma-ABT showed potent inhibitory effect on adjuvant primary inflammation and almost totally inhibited the secondary lesions. gamma-ABT improved the changes in lymphoid organ weight except of the thymus. gamma-ABT improved the change in albumin/globulin ratio, which is a parameter of systemic inflammatory reaction but did not improve the body weight gain in AID and normal rats. In addition gamma-ABT did not affect directly T or B lymphocytes as shown by the lymphocyte responses to mitogen (Con A) and a T cell dependent antigen (SRBC) but rather inhibited the suppressor cells found in AID. Although structurally gamma-ABT is completely different from known non-steroidal anti-inflammatories, immunosuppressive drugs behave to a great extent like them.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibody Formation; Antibody-Producing Cells; Arthritis, Experimental; B-Lymphocytes; Body Weight; Concanavalin A; Female; Foot; Liver Glycogen; Male; Mitogens; Mycobacterium; Rats; Rats, Inbred F344; T-Lymphocytes; Thiophenes

Stress usually has a depressing effect on immune function. However, we observed apparent immune enhancement following restraint stress. Fischer 344 rats were restrained in snug--fitting wire mesh tubes for 14 hr/day during the light portion of a daily 14:10 hr light/dark cycle for 0, 11, 22, or 33 days. Animals were sacrificed immediately after the last restraint session, and trunk blood and spleens were collected. Blood neutrophil percent was significantly higher after 11 or 22 days of restraint than in controls, as expected, and returned to baseline at 33 days. However, natural killer activity of spleen cells against Yac-1 targets, measured by a lactate dehydrogenase (LDH) release assay, was higher than controls after all periods of restraint, and especially after 11 days. Responses to concanavalin A by spleen cells from restrained rats were also higher than controls after all periods of restraint.

Topics: Animals; Body Weight; Concanavalin A; Female; Killer Cells, Natural; Leukocyte Count; Lipopolysaccharides; Lymphocyte Activation; Male; Rats; Rats, Inbred F344; Restraint, Physical; Spleen; Stress, Physiological

Vitamin D deficiency has pronounced growth retardation effects on the skeletal system. Because the immune system has been implicated in the regulation of bone metabolism, we examined the effect of vitamin D deficiency on the functional development of immune function in a rachitic rat model. Rats deprived of vitamin D3 both in utero and in postnatal life (-/-) had significantly reduced thymocyte or splenocyte [3H]-thymidine incorporation to mitogens and decreased macrophage chemotaxis when compared with vitamin D3-sufficient rats (+/+). Rats that were deficient in vitamin D3 only during in utero development (-/+) or during postnatal life (+/-) tended to have [3H]thymidine incorporation levels that were intermediate to those of the -/- and +/+ group. Similarly, the chemotactic response of macrophages from the +/- and -/+ groups was intermediate to that of the -/- and +/+ group, except at high concentrations of C5a in which there was an overlap with the +/+ group. Interestingly, secretion of soluble mediators, including interleukin 2 by lymphocytes and interleukin 1 and PGE2 by macrophages, was unaffected by vitamin D deficiency. These results suggest that vitamin D3 is essential for the normal development of certain biological responses of lymphocytes and macrophages. Moreover, this rachitic rat model system will enable further evaluation of the role of vitamin D in the functional development of the cells of the immune system and their relationship to skeletal growth.

Topics: Animals; Body Weight; Calcium; Cells, Cultured; Chemotaxis; Concanavalin A; Female; Lymphocyte Activation; Lymphocytes; Macrophages; Male; Phosphates; Phytohemagglutinins; Pregnancy; Rats; Spleen; Thymus Gland; Vitamin D Deficiency

Chickens were given daily injections of cyproterone acetate (CA) and the effects on plasma corticosterone, bodyweight, weights of the adrenals and lymphoid organs, numbers of circulating peripheral blood lymphocytes and their proliferation in the presence of lectins, concanavalin A (Con A) and phytohaemagglutinin (PHA), were investigated. Five daily doses of 10 or 30 mg CA kg-1 bodyweight each week over a three-week period caused a decrease in weight gain and a reduction in the relative weights of the bursa and thymus but not the spleen. There was a small decrease in the adrenals after treatment with 10 mg CA kg-1. When daily injections of CA were given over a seven-day period doses of 6 and 10 mg CA kg-1 bodyweight caused a significant (P less than 0.05) decrease in plasma corticosterone concentration after four days. However, after eight daily injections of CA a single injection of corticotrophin (10 iu ACTH kg-1) increased circulating corticosterone indicating CA had not completely blocked adrenal synthesis. CA had no effect on numbers of circulating peripheral blood lymphocytes or their ability to proliferate in the presence of Con A or PHA. The results indicate that CA is effective in lowering circulating corticosterone in the fowl but this did not affect the numbers or responsiveness of peripheral blood lymphocytes.

Topics: Adrenocorticotropic Hormone; Animals; Body Weight; Cell Count; Chickens; Concanavalin A; Corticosterone; Cyproterone; Cyproterone Acetate; Female; Lectins; Lymphocyte Activation; Lymphocytes; Male; Organ Size; Phytohemagglutinins

Propanil is a herbicide that is used extensively in rice farming to kill weeds without damaging the rice plant. The immunotoxic effects of acute exposure to propanil were determined in adult C57Bl/6 female mice exposed intraperitoneally to propanil at doses of 0, 10, 25, 50, 100, 200, or 400 mg/kg body wt. One week following exposure, the immune competency of the animals was assessed. Contact hypersensitivity response (CHR), blastogenic response to T- and B-cell-specific mitogens, and mixed lymphocyte reaction (MLR) were significantly depressed only in propanil-treated animals at 400 mg/kg. However, the number of splenic antibody-producing cells was also significantly depressed in a dose-dependent manner at the lower doses of 50, 100, and 200 mg/kg. In addition, a significant reduction in the thymus weight and an increase in absolute and relative spleen weight were also measured in animals treated with 200 and 400 mg/kg. The increase in spleen weight also showed a concomitant rise in spleen cellularity. These data indicate that propanil has a dose-dependent immunotoxic effect on the adult mouse that affects primarily the humoral response.

Topics: Anilides; Animals; Body Weight; Concanavalin A; Dermatitis, Contact; Female; Immunity; Mice; Mice, Inbred C57BL; Organ Size; Propanil; Spleen

Effect of treatment of female rats with an oral contraceptive agent (OCA), Ovulen-50, for 7 weeks on agglutination of hepatocytes with concanavalin A (con A) and activities of certain tumor marker enzymes were examined to find out if OCA treatment is related to preneoplastic or neoplastic processes. Hepatocytes from regenerating and nonregenerating livers of control female rats showed negligible agglutination with Con A, whereas hepatocytes from non regenerating but not from the regenerating livers of female rats treated with a combination of 5 micrograms ethinyl estradiol and 100 micrograms ethynodiol diacetate showed agglutination. Of the tumor marker enzymes such as hepatic glucose 6-phosphatase, gamma-glutamyl transpeptidase (gamma-GT), and arginase examined in the liver, only gamma-glutamyl transpeptidase showed a significant increase in activity in the steroid-treated rats. Plasma alkaline phosphatase activity was also higher in the treated animals. However, the magnitude of the changes observed was relatively small and perhaps unrelated to the neoplastic process.

Topics: Animals; Biomarkers, Tumor; Body Weight; Cell Aggregation; Concanavalin A; Contraceptives, Oral, Hormonal; Female; Hepatectomy; Liver; Liver Neoplasms, Experimental; Liver Regeneration; Organ Size; Rats; Rats, Inbred Strains

The response of lymphocytes to concanavalin A (Con A) was examined in the functionally hypothyroid SLD strain and the normal K strain chickens which were fed diets with or without T3 supplementation (0.1, 0.5 and 1.0 ppm) since the time of hatch. Peripheral blood lymphocytes (PBL) from 3 and 12 week old male and female chickens were incubated with Con A for 60 h. Mitogenic responsiveness was assessed by measuring the uptake of 3H-thymidine during the last 24 h of incubation. There was no difference in the mitogen response between male and female chickens. The mitogen responsiveness of PBL from the K strain tended to be greater than that from the SLD strain at both ages. The lowest dose of T3 (0.1 ppm) had no effect on the mitogen response of 3-week-old K strain chicks but caused an increase in mitogen response in 3-week-old SLD and in 12-week-old birds of both strains. Supplementation with 0.5 and 1.0 ppm T3 tended to decrease mitogen responsiveness in the K and SLD strain at both ages. The effect of treatment on thymus weights, bursa weights, and lymphocyte concentrations of the blood was also assessed.

Topics: Animals; Body Weight; Chickens; Concanavalin A; Female; Hypothyroidism; Leukocyte Count; Lymphocyte Activation; Lymphoid Tissue; Male; Organ Size; Poultry Diseases; Sex Factors; T-Lymphocytes; Triiodothyronine

Genes in the major histocompatibility complex (H-2) of the mouse control several immune functions as well as various facets of testosterone (Te) physiology. In order to study the genetic control of Te-induced immune suppression, complete Freund's adjuvant (CFA; containing Mycobacteria tuberculosis) was administered parenterally to several mouse strains differing at the H-2 complex which were either sham- or Te-treated. The specific lymphocyte proliferative response to purified protein derivative (PPD) was measured in draining lymph node cells. The response to PPD in strains bearing H-2b (B6 and B10) but not H-2d (B10.D2 and DBA/2) or H-2k (B10.BR and AKR) haplotypes was markedly lower in Te-implanted compared to sham-implanted controls. This result suggests that the ability of Te to dampen the immune response to PPD is regulated by H-2-linked gene(s).

Topics: Animals; Body Weight; Concanavalin A; H-2 Antigens; Immune Tolerance; Lymphocyte Activation; Male; Mice; Mice, Inbred Strains; Phytohemagglutinins; Seminal Vesicles; Species Specificity; Testosterone; Tuberculin

We have studied the effect of thyroid disfunction during the postnatal period, on the serum and brain levels of rat alpha-fetoprotein (AFP) and albumin. Hypothyroidism was induced by treatment of pregnant rats and their newborn pups with 2-mercapto-1-methylimidazole(methimazole). Hyperthyroidism was provoked in newborns by daily injections of thyroxine (0.25 micrograms/g body wt) from the 3rd postnatal day weaning. Impaired growth, lower brain size, altered behaviour and morphological features observed were according to an altered thyroid status. Hypothyroid rats showed a significantly reduction in serum AFP concentration (78% of control values at 8 days of age) and a slight increase in that of albumin. level could be appreciated. Thyroxine supplementation (0.2 micrograms/rat/day) corrected most of these alterations. Hyperthyroidism induced a drastic fall in both serum and brain AFP levels (about 48% of the corresponding control values). Albumin concentration in serum was augmented significantly from the 12th postnatal day, but its brain levels did not change significantly. In hyperthyroid rats, a significant reduction (37% relative to controls) in the concanavalin A-non reactive microform of AFP, was observed. This alteration of the glycosylation pattern of AFP could be due to the inhibition by thyroxine of the activity of the hepatic enzyme GlcNAc-transferase III.

Topics: Aging; alpha-Fetoproteins; Animals; Animals, Newborn; Body Weight; Brain; Concanavalin A; Glycosides; Hyperthyroidism; Hypothyroidism; Immunoelectrophoresis, Two-Dimensional; Rats; Rats, Inbred Strains; Serum Albumin; Thyroxine

The proliferative response of spleen cells from neonatally capsaicin-treated mice to 5 mitogens (LPS, PWM, dextran sulfate, ConA and PHA) were tested. Both B- and T-lymphocyte responses were essentially unaffected by the capsaicin treatment, which is known to destroy certain small-sized neuropeptide containing primary sensory neurons. However, the capsaicin-treated mice displayed a shift in the dose response to PHA so that the maximal response was obtained with a lower dose of the mitogen. The results exclude major effects of the affected sensory neurons on the development or expression of immune competence, but point to a possible modulatory effect on some step in the response to PHA.

Topics: Animals; Animals, Newborn; B-Lymphocytes; Body Weight; Capsaicin; Concanavalin A; Dextran Sulfate; Dextrans; Dose-Response Relationship, Drug; Lipopolysaccharides; Lymphocyte Activation; Mice; Mitogens; Organ Size; Phytohemagglutinins; Pokeweed Mitogens; Spleen; T-Lymphocytes

The ability of lymphocytes from newborn calves to undergo blastogenic responses to the mitogens Concanavalin A (Con A), phytohemagglutinin (PHA), or Pokeweed Mitogen (PWM), and immunomodulation of these responses by neonatal calf serum was assessed as a function of age. Lymphocytes were obtained from thymus, spleen, and mesenteric lymph nodes of 1-, 2- to 3-, 5- to 7-, and 9- to 10-d-old calves, aliquoted and incubated (+/- mitogens) in sera from 1-, 2-, 3-, or 7- to 10-d-old calves. Lymph-node lymphocytes responded least when cultured in sera from 1-d-old calves, regardless of mitogen or age of cell donor; the response increased as age of serum donor increased (P less than .05). Splenic lymphocytes responded similarly (P less than .005). However, when cultured in sera from older calves, splenic lymphocytes from older calves responded greater to PWM than did those from younger calves. Thymic lymphocytes responded minimally to PWM and PHA. Their response to Con A increased (P less than .005) with age of serum donor calf, but the effect was greatest on lymphocytes from 5- to 7-d-old calves. Mixing experiments with varying ratios of 1-d-old calf serum: 10-d-old calf serum suggested that serum from 1-d-old calves contained suppressive activity. Serum cortisol level (measured by radioimmunoassay) was 30 +/- 4.6 ng/ml in calves at 6 h of age and declined to 5.5 +/- 1.1 ng/ml by 10 d. Charcoal treatment to remove steroids did not enhance blastogenesis. Addition of cortisol (50 ng/ml) to charcoal-treated sera resulted in inhibition of response to PHA, but no change in response to Con A or PWM. Further investigation is indicated to characterize this immunosuppressive activity and to establish its relationship to disease susceptibility.

Topics: Age Factors; Animals; Animals, Newborn; Body Weight; Cattle; Concanavalin A; Hydrocortisone; Lymphocyte Activation; Lymphocytes; Organ Size; Phytohemagglutinins; Pokeweed Mitogens; Spleen; Thymus Gland

The immune status of rats fed a vitamin A-deficient diet (-A) was studied before they reached the weight plateau (stage 1), during the first 5 d of the weight plateau (stage 2) and during late stages of vitamin A deficiency (stage 3). Compared to vitamin A-supplemented (+A) animals, there were no significant differences in the relative splenic weights during the early and later stages of deficiency, but the total yield of isolated splenocytes was lower in -A rats during stages 2 and 3. The weights of the cervical and mesenteric lymph nodes were higher during the later stages of deficiency. In the spleen, concanavalin A (Con A)-induced responses were significantly depressed in -A rats at all three stages of deficiency. In stages 2 and 3 splenic pokeweed mitogen (PWM) responses were lower in -A than in +A rats. There were no changes in lymph node responses in stage 1. The Con A and PWM-induced responses of cervical lymph nodes of -A animals were higher in stages 2 and 3. Mesenteric lymph node responses were also higher in -A rats in stage 3. The alterations in the transformation responses of -A rats could not be explained by changes in the relative proportions of T-cell subsets.

Topics: Animals; Body Weight; Concanavalin A; Liver; Lymph Nodes; Lymphocyte Activation; Organ Size; Pokeweed Mitogens; Rats; Rats, Inbred Lew; Spleen; T-Lymphocytes; Thymidine; Vitamin A; Vitamin A Deficiency

The effect of 20 g/100 g diet of lactalbumin (L), casein (C), soy (S) and wheat (W) protein on the immune responsiveness of C3H/HeN mice has been investigated by measuring the humoral immune response to the T cell-independent antigen, TNP-Ficoll. The humoral immune response of mice fed the L diet was found to be higher than that of mice fed the C, S and W diets. On the other hand, delayed-type hypersensitivity, and splenic cell mitogen responses to phytohemagglutinin and concanavalin A did not differ among mice fed the various diets. Similarly, the type of diet did not appear to influence host resistance to Salmonella typhimurium. It is postulated that the type of protein in the diet influences directly the intrinsic capacity of the B lymphocytes to respond to an immunogenic stimulus.

Topics: Analysis of Variance; Animals; Antibody Formation; B-Lymphocytes; Body Weight; Concanavalin A; Dietary Proteins; Hypersensitivity, Delayed; Immunity, Cellular; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Phytohemagglutinins; Salmonella Infections; Spleen; T-Lymphocytes

Protein-deficient weanling rats fed on a 30 g casein/kg diet for 3 weeks lost albumin but maintained the level of serum alpha-1-antitrypsin, the most abundant protease inhibitor in blood. alpha-1-Antitrypsins from malnourished rats and control rats (given 250 g casein/kg diet) differed; the protease inhibitor from protein-deficient animals: (1) was more acidic, (2) appeared slightly larger (57 400 v. 56 000 daltons) on sodium dodecyl sulphate (SDS)-polyacrylamide gels, (3) had a more acidic Pi type and increased anodal mobility at pH 8.9, (4) bound more concanavalin-A and contained more carbohydrate, specifically two to three extra sialic acid residues. The amino sugar and neutral sugar contents of both preparations of alpha-1-antitrypsin were the same. Analysis of the products of cyanogen-bromide cleavage revealed that alpha-1-antitrypsin preparations from protein-deficient rats contain an extra glycopeptide that was not present in alpha-1-antitrypsin from control animals. In vivo studies showed that the increased sialic acid content of alpha-1-antitrypsin of protein-deficient rats did not alter the half-life of the molecule in the blood of control rats. However, the fractional catabolic rate of alpha-1-antitrypsin from either well-nourished or protein-deficient rats was significantly (P less than 0.01) lower in protein-deficient rats than in control rats (0.0247/h v. 0.0406/h). The decreased fractional catabolic rate could not be explained by changes in hepatic mannosyl-, galactosyl- or N-acetylhexosaminyl receptors since liver perfusion studies showed that bovine serum albumin, when covalently modified separately with each of these ligands, was extracted from the perfusion medium as rapidly or more rapidly by livers from malnourished animals. Perfused livers from protein-deficient rats secrete three times more alpha-1-antitrypsin than do livers from well-nourished animals. The decreased fractional catabolic rate and increased rate of biosynthesis and secretion of the glycoprotein by livers from protein-deficient animals may account for the maintenance of alpha-1-antitrypsin levels during protein malnutrition.

Topics: Albumins; alpha 1-Antitrypsin; Amino Acids; Animals; Asialoglycoproteins; Body Weight; Carbohydrates; Concanavalin A; Cyanogen Bromide; Electrophoresis; Glycoproteins; Iodine Radioisotopes; Liver; Orosomucoid; Protein Deficiency; Rats; Serum Albumin; Weaning

The effect of 20 g/100 g dietary lactalbumin (L) or casein (C) diets or a nonpurified (NP) diet on the immune responsiveness of C57Bl/6J, C3H/HeJ and BALB/cJ mice has been investigated by measuring the response to the T cell-independent antigen, TNP-Ficoll. To investigate the possible influence of dietary protein type on the supply of B lymphocytes, bone marrow lymphocyte production has been examined by a radioautographic assay of small lymphocyte renewal and an immunofluorescent stathmokinetic assay of pre-B cells and their proliferation. The humoral response of all mice fed the L diet was found to be higher than that of mice fed the C diet or nonpurified diet. A similar pattern of dietary protein effect in (CBA/N X DBA/2J) F1 mice carrying the xid defect was observed following challenge with sheep red blood cells (SRBC). An even greater enhancing effect of dietary L was noted in normal (DBA/2J X CBA/N) F1 mice after immunization with SRBC, but in contrast, the normal large-scale production of B lymphocytes in mouse bone marrow was independent of the type of dietary protein. Dietary protein type did not affect blood level of minerals and trace metals. The free plasma amino acid profile essentially conformed to the amino acid composition of the ingested protein, suggesting that the changes in plasma amino acid profile might be a crucial factor in diet-dependent enhancement or depression of the B-cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibody Formation; Autoradiography; B-Lymphocytes; Blood Chemical Analysis; Body Weight; Bone Marrow; Concanavalin A; Dietary Proteins; Fluorescent Antibody Technique; Immunity, Cellular; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Phytohemagglutinins; Salmonella Infections; Spleen; T-Lymphocytes; Thymidine; Tritium

C57BL/6 mice were administered 50 or 200 ppm of Cd as CdCl2 in the drinking water for either 3 to 4 (short term) or 9 to 11 (long term) weeks. In other experimental designs, mice were exposed orally to 300 ppm of Cd or injected with 2.5 mg/kg of Cd ip. The proliferative response to the T cell mitogens Con A and PHA was increased in cultures of spleen cells from orally treated mice in most of the experiments performed. After primary immunization with sheep red blood cells, the number of IgM antibody forming cells per 10(7) spleen cells was also moderately higher in mice exposed to 50 or 200 ppm of Cd for short or long term. In contrast, long-term exposure to 300 ppm of Cd depressed the antibody response to SRBC. Administration of ZnCl2 prevented the enhancement of the PFC response in mice orally administered 50 ppm of Cd. The capacity to suppress the antibody response of spleen cells preincubated with sodium periodate was decreased after short-term oral or ip. Cd administration but was completely or partially recovered after long-term exposure to either 50 or 200 ppm of Cd.

Topics: Animals; Body Weight; Cadmium; Concanavalin A; Dose-Response Relationship, Drug; Hemolytic Plaque Technique; Immunity; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Species Specificity; Spleen; T-Lymphocytes, Regulatory; Zinc

Seven weeks after orchiectomy, 19 and 10 month old mice had mean thymic weight increases of 34 and 128%, respectively, compared to sham-operated controls. Peripheral WBC counts were greater (p less than .05) in castrates of both age groups. On a cell for cell basis, the mitogen response of castrate spleen cells was not significantly greater than controls, and in some instances was significantly less. Although individual cell function may not be augmented after castration, in vivo immune response may be potentiated due to an increase in absolute number of lymphoid cells.

Topics: Aging; Animals; Body Weight; Castration; Concanavalin A; Leukocyte Count; Lipopolysaccharides; Male; Mice; Mitogens; Phytohemagglutinins; Spleen; Thymus Gland

Iron-deficiency anemia impaired the blastogenic response of splenic lymphocytes and partially purified T cells to Concanavalin A and phytohemagglutinin. The response of splenic lymphocytes and partially B cells to bacterial lipopolysaccharide was also significantly impaired. Caloric restriction in pair-fed mice did not have any significant effect. Blastogenic response to the three mitogens was restored to normal after anemic mice were fed the regular diet containing 25 to 30 mg Fe/kg (FeSO4) for approximately 10 days. We also found that in the anemic mice the mean wet weights per 100 g of body of spleen, heart, brain, and kidney increased, while those of the thymus and liver decreased. In the pair-fed mice only the mean wet weight of the liver significantly decreased. There was a small but significant decrease in the white blood count and peripheral lymphocyte count in the anemic but not the pair-fed mice. The mechanism by which iron deficiency impairs the cell-mediated immune response is discussed.

Topics: Anemia, Hypochromic; Animals; B-Lymphocytes; Body Weight; Cells, Cultured; Concanavalin A; Female; Ferrous Compounds; Iron; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Organ Size; Phytohemagglutinins; Spleen; T-Lymphocytes

A toxin associated with Toxoplasma gondii infection was obtained from the trophozoites and culture medium used to propagate the parasite in cell cultures. The toxin, named Toxofactor (TF), administered parenterally or nonparenterally in adult mice, produces transient symptoms of lethargy, ruffled fur, and body weight loss. Organ changes which accompanied the outward symptoms included hepatosplenomegaly and involuted thymus. TF activity was detected in extracts of the blood, peritoneal fluid, liver, and spleen of infected mice. Severe damage to embryonal and fetal development was induced when TF was administered during pregnancy. Resorption, abortion, and congenital abnormalities were produced, dependent upon the stage of development at the time of exposure. Adult mice which had reacted to and recovered from an initial intraperitoneal injection to TF were protected against a secondary challenge from TF. Fetal development was also protected from damage when TF was used to challenge adults previously exposed to TF. Mouse and rabbit anti-TF sera neutralized TF activity in the adult. In no instance did control mice show any deleterious effect when exposed to soluble cell lysate from the uninfected cell line (BHK-21) used to propagate the organism plus the used medium from these same uninfected cells. TF activity was not attributed to bacterial, myocoplasmal, or viral contamination. TF toxic activity is labile to elevated temperature and high or low pH, which also destroy its protective properties. TF activity was sensitive to trypsin and was obtained in the elution fraction (alpha-methyl-D-mannoside) from affinity chromatography (concanavalin A-Sepharose 4B). Ultrafiltration indicated the molecular weight to be between 50,000 and 100,000. TF, apparently a glycoprotein, was quantitated for activity by a weight loss assay. A unit of activity was defined as the minimum quantity of TF (highest dilution) which produced at least a 10% average body weight loss in adult Nya:NYLAR female mice between days 7 and 12 post-intraperitoneal injection.

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Cells, Cultured; Concanavalin A; Female; Hydrogen-Ion Concentration; Mice; Mice, Inbred Strains; Molecular Weight; Pregnancy; Reproduction; Temperature; Toxins, Biological; Toxoplasmosis, Animal

Seventeen young male subjects underwent a six-week training period and their physical fitness was examined using a bicycle ergometer test. Twelve subjects without any marked training served as controls. Venous blood was drawn immediately before and after exercise on a bicycle ergometer both before and after training. After exercise, the subjects developed a leukocytosis as well as lymphocytosis where the proportion of E-rosettes, theophylline resistant E-rosettes and SIg-positive cells remained stable but their absolute number rose by more than 100% before training and more than 50% after training. In spite of the rise of immunocompetent cells in the circulation, the post exercise increase of lymphocyte transformation was not more than 10% both before and after training. After training the response to physical stress is manifested by a significantly weaker mobilization of lymphocytes into the circulation than before training. Consequently, when physical fitness is high fewer immunocompetent cells are required to produce a normal immune response than when physical fitness is low. Our findings indicate that in healthy individuals improved physical fitness compensates for the influence of stress on the immune system.

Topics: Adolescent; Adult; Body Weight; Concanavalin A; Exercise Test; Heart Rate; Humans; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Physical Education and Training; Phytohemagglutinins

Topics: Animals; Antibody Formation; Body Weight; Chickens; Concanavalin A; Hyperthyroidism; Immunity; Male; Organ Size; Propylthiouracil; Spleen; Thymus Gland; Thyroid Gland; Thyroxine

Intrauterine thymectomy was carried out on days 36, 40, 48 and 68 (neonatal) of foetal life to investigate the role of thymus and emigration of thymocytes in the development of mitogenic (PHA, Con A, DxS) responses in the guinea pig. The results provide further evidence that emigration of thymocytes is a continuous process which takes place already at the time of demarcation between thymic cortex and medulla (before day 36 of gestation) and again immediately after birth. In the lymph nodes of guinea pigs thymectomized on day 36 in utero a small PHA and Con A responding cell population exists at the time of birth but not any more 3-4 mth later. This population is considered to depend on the transplacental thymic product(s). However, spleen and blood lymphocytes of animals thymectomized on day 36 in utero respond to PHA and Con A to some extent at the age of 3-4 mth, suggesting that the population emigrating before day 36 has a longer survival in the spleen and blood than in lymph nodes. Thymectomy at 40 days of gestation leaves an additional population which can express a good PHA and Con A response even in lymph nodes without a direct thymic influence. Responses to DxS were not significantly affected by the intrauterine thymectomy. Thus, intrauterine thymectomy at 36 days of gestation induces a severe but not complete T cell depletion in the guinea pig.

Topics: Animals; Animals, Newborn; Body Weight; Concanavalin A; Dextrans; Female; Guinea Pigs; Leukocyte Count; Lymph Nodes; Lymphocyte Activation; Lymphocytes; Mitogens; Phytohemagglutinins; Postoperative Complications; Pregnancy; Rosette Formation; Spleen; Thymectomy; Uterus

Topics: Animals; Body Weight; Cell Count; Cell Division; Cell Movement; Concanavalin A; Dietary Proteins; Lymph Nodes; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Phytohemagglutinins; Protein-Energy Malnutrition; Spleen; Thymus Gland; Time Factors

Although PGE1, in pharmacologic quantities, possesses significant in vivo immune-modulating activities, its effects on different lymphoid populations have not been defined. In the present study, lymphocyte numbers, turnover rates, and functional activities were assessed in Swiss-Webster mice receiving PGE1, 200 microgram twice daily, for up to 14 days. The most pronounced cellular alterations were observed in the thymus. After 2 wk, the number of theta-positive cells decreased by 81%. Total splenic cellularity was concomitantly reduced by 28%. This was primarily due to a loss of B lymphocytes; the number of these cells decreased by 40%. Bone marrow lymphocytes were also decreased by PGE1 administration. By contrast, peripheral blood lymphocytes and splenic T cells were not significantly altered. Similar changes in lymphocyte numbers were observed in adrenalectomized mice, indicating that depletion was not due to a corticosteroid effect. In normal mice, PGE1 reduced the in vivo incorporation of 3HTdr in both the thymus and the spleen by approximately 50%; this finding, in conjunction with histologic and cytologic observations, suggests a decrease in intrinsic rates of lymphopoiesis. Residual splenocytes were not impaired in their in vitro responses to three polyclonal mitogens: PHA, Con-A, and endotoxin. Studies in cortisol-treated mice showed that PGE1 caused a decrease in both steroid-sensitive and steroid-resistant thymocytes and splenocytes.

Topics: Adrenalectomy; Animals; B-Lymphocytes; Body Weight; Concanavalin A; Corticosterone; Female; Hydrocortisone; Indomethacin; Leukocyte Count; Lymphocytes; Mice; Prostaglandins; Prostaglandins E; Spleen; T-Lymphocytes; Thymidine; Thymus Gland

The immunosuppressive effect of cyclosporin A (CS-A) was investigated in RIC-Sprague-Dawley rats. In vivo, CS-A totally abolished the formation of antibodies to the hapten dinitrophenyl (DNP) in rats immunized with DNP-keyhole limpet haemocyanin. In vitro, the effect of CS-A was investigated in spleen cell cultures stimulated by concanavalin A, phytohaemagglutinin or lipopolysaccharide. The suppression due to CS-A was more pronounced in cultures set up with cells from rats fed the drug than in spleen cell cultures from control animals supplemented with serum containing CS-A. Purified by filtration through Degalan-rat Ig-anti IgG columns, T lymphocytes from CS-A treated rats were no longer suppressed by CS-A serum in contrast to purified T cells obtained from control rats. Thus, CS-A seems to interfere with the mitogenic triggering of a subpopulation of T lymphocytes resulting in a functional clonal deletion.

Topics: Animals; Antibody Formation; Body Weight; Concanavalin A; Immunosuppressive Agents; Lipopolysaccharides; Lymphocyte Activation; Lymphocyte Cooperation; Peptides, Cyclic; Phytohemagglutinins; Rats; Rats, Inbred Strains; T-Lymphocytes

Topics: Animals; B-Lymphocytes; Body Weight; Cell Count; Cell Division; Concanavalin A; Female; Fetus; Lipopolysaccharides; Liver; Lymphocytes; Male; Mice; Mice, Inbred CBA; Mitosis; Organ Size; Pregnancy; Spleen; T-Lymphocytes; Thymus Gland

The effect of vitamin A deficiency on the response of splenic lymphocytes to mitogenic stimulation was determined in an experimental rat model. Male Lewis rats were divided into three groups. The ad libitum group (AL) was fed unlimited amounts of a vitamin A-supplemented diet. The vitamin A-deficient group (DEF) received a commercial vitamin A-free diet. The pair-fed group (PF) received a vitamin A-containing diet equivalent in amount to that consumed by the DEP group. During the early stages of vitamin A deficiency (determined by cessation of weight gain), the rats were killed and the isolated splenic lymphocytes subjected to mitogenic stimulation. Lymphocytes from DEF rats had one-third the transformation response to the mitogens Concanavalin A, Phytohemagglutinin and E. coli Lipopolysaccharide S of the AL and PF groups. When the DEF rats were supplemented with vitamin A, the transformation response returned to control values within 3 days. In addition to the alterations in the immune response, the DEF rats showed a marked leukopenia, a decrease in the number of circulating lymphocytes and an increase in the number of circulating neutrophils.

Topics: Animals; Blood Cell Count; Body Weight; Concanavalin A; Immunity, Cellular; Lipopolysaccharides; Lymphocyte Activation; Male; Organ Size; Phytohemagglutinins; Rats; Spleen; Vitamin A; Vitamin A Deficiency

The effect of fat feeding on adipocyte insulin binding was examined to expand a study of adaptive changes in plasma membrane functions. Cells from rats fed a high fat (L) diet for five to seven days bound less insulin and showed a decreased response to insulin (glucose oxidation) compared to those from rats fed a high glucose (G) diet. Both high and low affinity sites were influenced; the extent of the binding difference increased as increasing concentrations of insulin were present in the assay medium. Diet did not change hormone degradation on the capacity of phospholipase C to increase binding. Concanavalin A effects on fat cells were also decreased by L diet both in inhibition of insulin binding and its insulin-like effect on glucose oxidation. Spermine, which had no effect on insulin binding, also had a smaller insulin-like effect on glucose oxidation by L cells than by G cells. Serum insulin was significantly lower (30 +/- 3.7 muU/ml) in L than in G (43 +/- 3.1 muU/ml) groups. Dietary fat produces alterations in fat cells that decrease insulin binding as a part of a complex overall adaptation to the diet.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Concanavalin A; Dietary Carbohydrates; Dietary Fats; Glucose; Glycolysis; Insulin; Kinetics; Male; Phospholipases; Rats; Receptor, Insulin

Topics: Age Factors; Animals; Animals, Newborn; Antibody Formation; Antigens; Antigens, Bacterial; B-Lymphocytes; Body Weight; Bone Marrow Cells; Bone Marrow Transplantation; Brucella abortus; Bursa of Fabricius; Chickens; Chimera; Concanavalin A; Cyclophosphamide; Erythrocytes; Floxuridine; Idoxuridine; Immunologic Deficiency Syndromes; Iodine Radioisotopes; Lectins; Lymphocyte Activation; Lymphocyte Transfusion; Plant Lectins; Radiation Chimera; Sheep; Spleen; T-Lymphocytes; Thymus Gland; Transplantation, Homologous

Functional immune changes were monitored in populations of the long-lived C57BL/6J strain of mice which were subjected to dietary restriction from time of weaning or subjected to such restriction both before and after weaning, along with the appropriate control populations. Responses to T and B cell mitogens (PHA, Con-A, pokeweed, bacterial lipopolysaccharide, and PPD), to injected sheep red blood cells, and measurement of skin allograft rejection rates were followed. Early in life, restricted mice appear immunosuppressed, as judged by all these parameters. Skin allograft rejection remained suppressed until relatively late in life. Other responses tended to reverse from the earlier pattern; by mid-life restricted mice responded better than controls. Dietary restriction profoundly affects the immune system. Mice on such regimes display anatomic and certain immune functional changes which suggest that the immune system may mature less rapidly and stay "younger" longer than in the controls. Furthermore, dietary restriction results in prolongation of life span.

Topics: Animals; Body Weight; Concanavalin A; Diet; Dietary Proteins; Female; Hemolytic Plaque Technique; Immunity; Lectins; Life Expectancy; Lipopolysaccharides; Male; Mice; Mice, Inbred A; Mice, Inbred C57BL; Mitogens; Nutrition Disorders; Nutritional Requirements; Organ Size; Skin Transplantation; Spleen; T-Lymphocytes; Thymectomy; Transplantation, Homologous

Topics: Animals; Body Weight; Carcinoma; Concanavalin A; Female; Genotype; Graft vs Host Reaction; Hybridization, Genetic; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mononuclear Phagocyte System; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Organ Size; Spleen; T-Lymphocytes; Time Factors

Topics: Age Factors; Animals; Animals, Newborn; Antibody Formation; Body Weight; Concanavalin A; Culture Techniques; Graft vs Host Reaction; Histocompatibility; Histocompatibility Testing; Immunity, Cellular; Isoantigens; Lymphocytes; Mice; Mice, Inbred Strains; Mitomycins; Organ Size; Rats; Rats, Inbred Strains; Spleen; Splenomegaly; Staphylococcus; Thymidine; Thymus Gland; Tritium