concanavalin-a and Sepsis

We recently reported that after LPS stimulation, IL-37 translocates to the nucleus and reduces the expression of proinflammatory cytokines. The aim of this study was to investigate whether transiently expressed IL-37 in mice reduces inflammation in concanavalin A (ConA)-induced hepatitis and LPS-induced sepsis. Transgene IL-37 expression was detected in the liver lysate of mice injected with IL-37 plasmid-DNA after hydrodynamic tail vein injection. All mice developed severe acute hepatitis after ConA injection. No difference in the histological score and serum ALT was observed between the two groups that might be explained by patchy expression of IL-37 protein in the liver. However, 2 hrs after ConA injection, serum levels for IL-1α, IL-6, IL-5, and IL-9 were significantly reduced in IL-37-expressing mice as seen for the LPS model. In conclusion, in vivo expression of human IL-37 in mice reduces local and systemic inflammation in ConA-induced hepatitis and LPS challenge.

Topics: Animals; Cloning, Molecular; Concanavalin A; Disease Models, Animal; Female; Gene Expression Regulation; Hepatitis; Immunohistochemistry; Inflammation; Injections, Intravenous; Interleukin-1; Lipopolysaccharides; Liver; Luciferases; Mice; Mice, Inbred C57BL; Plasmids; Sepsis; Time Factors; Transgenes

Caspases mediate essential key proteolytic events in inflammatory cascades and the apoptotic cell death pathway. Human caspases functionally segregate into two distinct subfamilies: those involved in cytokine maturation (caspase-1, -4 and -5) and those involved in cellular apoptosis (caspase-2, -3, -6, -7, -8, -9 and -10). Although caspase-12 is phylogenetically related to the cytokine maturation caspases, in mice it has been proposed as a mediator of apoptosis induced by endoplasmic reticulum stress including amyloid-beta cytotoxicity, suggesting that it might contribute to the pathogenesis of Alzheimer's disease. Here we show that a single nucleotide polymorphism in caspase-12 in humans results in the synthesis of either a truncated protein (Csp12-S) or a full-length caspase proenzyme (Csp12-L). The read-through single nucleotide polymorphism encoding Csp12-L is confined to populations of African descent and confers hypo-responsiveness to lipopolysaccharide-stimulated cytokine production in ex vivo whole blood, but has no significant effect on apoptotic sensitivity. In a preliminary study, we find that the frequency of the Csp12-L allele is increased in African American individuals with severe sepsis. Thus, Csp12-L attenuates the inflammatory and innate immune response to endotoxins and in doing so may constitute a risk factor for developing sepsis.

Topics: Africa; Alzheimer Disease; Animals; Apoptosis; Base Sequence; Black or African American; Case-Control Studies; Caspase 12; Caspases; Concanavalin A; Cytokines; Endoplasmic Reticulum; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Inflammation; Lipopolysaccharides; NF-kappa B; Polymorphism, Single Nucleotide; Primates; Sepsis

The operative procedure for thoracic esophageal cancer, including thoracotomy, laparotomy, and three-field lymph node dissection, is a particularly stressful surgery that is characterized by high morbidity and mortality. The aim of this study was to evaluate the immunologic and nutritional states of patients to determine possible predictive factors of morbidity and mortality in patients receiving thoracic esophagectomy. Patients receiving thoracic esophagectomy were retrospectively divided into two groups. One group had postoperative infectious complications (group C+, n = 27), and the other had no complications (group C-, n = 76). They were treated with total parenteral nutrition or enteral nutrition providing 35-40 kcal. kg(-1). d(-1) of energy and 1.3-1.5 kcal. kg(-1). d(-1) of amino acids throughout the study period. The phytohemagglutinin (PHA)- and concanavalin A (Con A)-induced proliferation of peripheral blood mononuclear cells (PBMC) from the patients were measured before and at days 7 and 21 after the operation. Serum albumin, prealbumin, transferrin, the retinol binding protein, and the C-reactive protein were also evaluated. Three patients out of 27 in group C+ died because of severe infectious complications, whereas none of patients was fatal in group C-. PHA- and Con A-induced proliferation of PBMC was significantly low before the operation and remained suppressed on the 21st postoperative day in group C+. No significant difference was observed in nutritional status during the perioperative days between the two groups. Our results indicate that esophageal cancer patients with preoperative suppression of the cell-mediated immunity can be identified as a higher risk population in the postoperative period. When adequate nutrition is received, however, the correlation between nutritional status and mortality disappears.

Topics: Blood Proteins; Concanavalin A; Enteral Nutrition; Esophageal Neoplasms; Esophagectomy; Female; Humans; Immunosuppression Therapy; Male; Middle Aged; Nutritional Status; Parenteral Nutrition, Total; Perioperative Care; Phytohemagglutinins; Preoperative Care; Retrospective Studies; Sepsis; Stress, Physiological

Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats.

Topics: Animals; Animals, Newborn; Bacteroides Infections; Calcium; Concanavalin A; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Escherichia coli Infections; Isoenzymes; Lymphocyte Activation; Membrane Proteins; Nitrobenzenes; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Resveratrol; Sepsis; Signal Transduction; Spleen; Stilbenes; Sulfonamides; T-Lymphocytes

To evaluate the effect of burn injury with and without an Escherichia coliseptic complication on T-cell proliferation, interleukin-2 production, and Ca(2+) signaling responses in intestinal Peyer's patch and splenic T cells.. Prospective, randomized, sham-controlled animal study.. University medical center research laboratory.. Adult male Sprague-Dawley rats.. Rats were subjected to a 30% total body surface area, full skin thickness burn. Infection in rats was induced via intraperitoneal inoculation of E. coli, 10(9) colony forming units/kg, with or without a prior burn.. Rat Peyer's patch and splenic T lymphocytes were isolated by using a nylon wool cell purification protocol. T-cell proliferation, interleukin-2 production, and Ca(2+) signaling responses were measured after stimulation of cells with the mitogen, concanavalin A. T-cell proliferation was determined by measuring incorporation of (3)H-thymidine into T-cell cultures. Interleukin-2 production by T-cell cultures was measured by using enzyme-linked immunosorbent assay. Intracellular T-cell Ca2(+ )concentration, [Ca(2+)](i), was measured by the use of Ca(2+)-specific fluorescent label, fura-2, and its fluorometric quantification. [Ca(2+)](i) was also evaluated by the use of digital video imaging of fura-2 loaded individual T cells. T-cell proliferation and interleukin-2 production were suppressed substantially in both Peyer's patch and splenic T cells 3 days after either the initial burn alone or burn followed by the E. coli inoculation at 24 hrs after the initial burn. There seemed to be no demonstrable additive effects of E. coli infection on the effects produced by burn injury alone. The T-cell proliferation and interleukin-2 production suppressions with burn or burn-plus-infection insults were correlated with attenuated Ca(2+) signaling. E. coli infection alone suppressed T-cell proliferation in Peyer's patch but not in splenic T cells at 2 days postbacterial inoculation; E. coli infection had no effect on Peyer's patch or splenic T cells at 1 day postinjury. On the other hand, burn injury alone caused a substantial T-cell proliferative suppression at 2 days postburn in both Peyer's patch and splenic cells and a significant suppression in T-cell proliferation on day 1 postburn in Peyer's patch but not in the spleen.. An initial burn injury suppressed T-cell proliferation at a level that it would not be further affected by a subsequent infection even if the infection by itself has the potential of suppressing T-cell proliferation. An earlier onset of T-cell suppression in Peyer's patch cells than in the spleen with burn could be attributable to an initial hypoperfusion-related intestinal mucosal tissue injury. Overall, our study supports the concept that burn injury per se can significantly suppress T-cell mediated immunity and that the intestine is an early tissue site of such suppression.

Topics: Analysis of Variance; Animals; Burns; Calcium Signaling; Concanavalin A; Escherichia coli Infections; Immune Tolerance; Interleukin-2; Male; Peyer's Patches; Random Allocation; Rats; Rats, Sprague-Dawley; Sepsis; Spleen; Statistics, Nonparametric; T-Lymphocytes

To describe the alterations in circulating concentrations of immune cells as well as in in vitro mitogen-stimulated response in a recently developed rat model of intra-abdominal infection.. Randomized, controlled study.. Government research facility.. Male Sprague-Dawley rats.. Infected animals received an intraperitoneal infusion of 6.0 x 10(8) colony forming units of Escherichia coli during 12 hrs, whereas control rats received a sterile inoculum. All experimental animals underwent laparotomy and peritoneal lavage at the end of the infusion period. Blood samples were obtained 12 hrs, 36 hrs, or 7 days after the onset of infusion. Splenocytes were concomitantly harvested and assayed for response to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and lipopolysaccharides, as well as for production of interleukin (IL)-2.. Infected rats showed a marked leukopenia (-82% for 36 hrs), with leukocyte counts returning to normal at 7 days. They also developed a marked lymphocytopenia throughout the study; this was achieved through comparable reductions in circulating T and B cells. Con A responses in both groups were similar for 7 days. In contrast, splenocytes from infected animals showed reduced responses to lipopolysaccharides (-64%) and PHA (-30%) for 36 hrs compared with control splenocytes. IL-2 production from mitogen-stimulated splenocytes was suppressed in infected rats to 66% of that of control rats for 7 days. Suppressed PHA responses were not restored to control values in the presence of IL-2. For all of the parameters assessed, control animals showed either no significant changes or relatively fewer changes than infected rats.. This model of intra-abdominal infection is associated with changes in circulating concentrations of immune cells as well as with temporary functional defects in B and T cells, consistent with those often observed in patients with peritonitis. However, the role of IL-2 in limiting the adverse effects of infection in this experimental model seems to be limited. This model may be a useful tool in furthering our understanding of the pathophysiology of intra-abdominal infections and in assessing the efficacy of new therapeutic modalities.

Topics: Abdomen; Animals; B-Lymphocyte Subsets; Concanavalin A; Escherichia coli Infections; Flow Cytometry; Interleukin-2; Lipopolysaccharides; Male; Models, Immunological; Phytohemagglutinins; Rats; Rats, Sprague-Dawley; Sepsis; T-Lymphocyte Subsets

Studies have indicated that following the induction of sepsis, there is a late (24 h) generalized suppression of the immune response which is associated with increased anti-inflammatory mediator release (e.g., IL-10). However, the mechanisms by which this occurs are unknown. In this regard, recent studies indicate that p38 mitogen-activated protein kinase (p38 MAPK) may play a central role in transducing the signals from immunosuppressive agents which in turn may alter lymphoid cytokine release. The aim of this study, therefore, was to determine whether the anti-inflammatory mediator IL-10 alters splenocyte IL-2 and IFN-gamma release, as well as the expression and activation of p38 MAPK in septic animals.. Splenocytes (SPL) (or for some experiments purified T cells) were harvested from mice subjected 24 h earlier to either sepsis by cecal ligation and puncture (CLP) or Sham-CLP and stimulated with 2.5 microg concanavalin A (ConA)/ml in the presence or absence of either monoclonal antibody (Mab) to IL-10 (4 microg/ml) or IgG control. In subsequent studies, sepsis was induced in C57BL/6J and C57BL/6 IL-10 knockout mice, and SPL harvested and stimulated with ConA. SPL cytokine release was measured by ELISA, and the expression and phosphorylation of p38 MAPK were measured by Western analysis.. The results indicate that Th1 cytokine (IL-2, IFN-gamma) release was depressed by sepsis, while p38 MAPK expression and activity were increased in SPL as well as in T-cells. Neutralization of IL-10 by in vitro use of anti-IL-10 Mab and in the IL-10 knockout animal restored the Th1 response and caused a downregulation of p38 MAPK expression and activity after CLP. Thus, IL-10 appears to contribute to the increase in p38 MAPK activity and expression and the corresponding suppression of Th1 response seen in late sepsis.

Topics: Animals; Antibodies, Monoclonal; Calcium-Calmodulin-Dependent Protein Kinases; Cecum; Concanavalin A; Interferon-gamma; Interleukin-10; Interleukin-2; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Sepsis; Signal Transduction; Spleen

Recent studies suggest that increased lymphocyte apoptosis (Ao) detected in peripheral blood T cells from burn patients appears to contribute to decreased lymphocyte immunoresponsiveness. However, while it is known that sepsis induces a marked depression in the splenocyte immune response (i.e. decreased interleukin-2, interferon-gamma production and proliferation) in response to the T-cell mitogen concanavalin A (Con A), it is unknown whether this depression is associated with an increase in inducible Ao and if so, which mediators control this process. To assess this, splenocytes were harvested from mice at 24 hr (a period associated with decreased Con A response) after the onset of polymicrobial sepsis [caecal ligation and puncture (CLP)] or sham-CLP (Sham) and then stimulated with 2.5 microg Con A/ml (24 hr). Septic mouse splenocytes stimulated with Con A, while not showing a change in their phenotypic make-up, did exhibit a marked increase in the percentage of splenocyte that were Ao+ which was associated with altered cytokine release. This appears to be due to an increase in the percentage of Ao+ cells in the CD4+ CD8- population and was associated with enhanced Fas antigen expression as well as an increase in mRNA for the Fas-FasL gene family. To determine if the changes in Ao are due to either endotoxin (a product of Gram-negative bacteria seen in CLP mice) or the expression of Fas ligand (FasL; a mediator of activation-induced lymphocyte Ao), a second set of studies examining Con A-inducible Ao was performed with splenocytes harvested from septic endotoxin-tolerant C3H/HeJ and the FasL-deficient C3H/HeJ-Fasl gld mice. The results show that increased splenocyte Ao detected following CLP is due to a FasL-mediated process and not to endotoxin. Thus the inadvertent up-regulation of FasL-mediated splenocyte Ao may contribute to the depression of splenocyte immune responses seen during polymicrobial sepsis.

Topics: Animals; Apoptosis; CD4-Positive T-Lymphocytes; Cell Culture Techniques; Concanavalin A; Cytokines; Endotoxins; Fas Ligand Protein; fas Receptor; Humans; Lymphocyte Activation; Male; Membrane Glycoproteins; Mice; Mice, Inbred C3H; Sepsis; Spleen; Th1 Cells; Th2 Cells

Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family. Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated. The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha.

Topics: Aging; Animals; Base Sequence; Concanavalin A; Cytokines; DNA Primers; In Vitro Techniques; Inflammation Mediators; Lipopolysaccharides; Lymphotoxin-alpha; Lymphotoxin-beta; Membrane Proteins; Mice; Mice, Inbred BALB C; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sepsis; Spleen; Superantigens; Transcription, Genetic; Up-Regulation

Prostaglandin E2 (PGE2) has been known to modulate immune responses by inhibiting T-cell activation following hemorrhagic and traumatic injury. Recently, we documented a sepsis-related depression in concanavalin A (ConA)-induced T-cell proliferation and intracellular Ca2+ (Ca2+i) mobilization. The present study evaluated the potential role of PGE2 in the sepsis-related attenuation in Ca2+ signaling and proliferation in T cells. Sepsis was induced in rats by implanting into their abdomen fecal pellets containing Escherichia coli (150 CFU) and Bacteroides fragilis (10(4) CFU). A group of rats implanted with septic pellets were treated with indomethacin at three consecutive time points. Levels of PGE2 in blood were measured with a radioimmunoassay kit. ConA-induced [Ca2+]i mobilization in T cells obtained from indomethacin-treated and untreated rats was measured with Fura-2 and microfluorometry. We observed a 10-fold increase in PGE2 levels in the circulation of septic rats compared with levels in rats implanted with bacterium-free sterilized pellets. The proliferative response and Ca2+i mobilization were significantly depressed in T cells obtained from septic rats 48 h after implantations compared with those in rats implanted with sterile pellets. However, treatment of rats with the cyclooxygenase inhibitor indomethacin prevented the sepsis-related depression in ConA-induced T-cell Ca2+i mobilization as well as proliferation. Further, incubation of T cells from nonimplanted control rats with PGE2 resulted in a substantial depression in both T-cell proliferation and Ca2+i mobilization. The restoration of T-cell proliferation and Ca2+ signaling after indomethacin treatment of septic rats and the depression in the mitogen responsiveness in T cells previously exposed to PGE2 suggest that the PGE2 does play a significant role in the modulation of T-cell responses in septic rats and that such PGE2-induced suppression in T-cell activation is likely due to an attenuation in Ca2+ signaling.

Topics: Animals; Calcium; Concanavalin A; Dinoprostone; Indomethacin; Lymphocyte Activation; Male; Rats; Rats, Sprague-Dawley; Sepsis; T-Lymphocytes

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

Alterations in T-lymphocyte kinetics and/or activation have been implicated in burn and traumatic injury. This study evaluated concanavalin A (Con A) regulation of both intracellular Ca2+ (Cai2+) and proliferation in T-lymphocytes harvested from spleens of septic rats. Rats were implanted with fecal pellets containing Escherichia coli (150 colony forming units (CFU)) and Bacteroides fragilis (10(4) CFU). T-cell[Ca2+]i was measured before and after treatment of cells with ConA, using Fura-2 and microfluorophotometry. Splenic lymphocytes were cultured for 72 h with Con A to assess their proliferative response. As compared to sterile-implanted rats, the septic rat T-lymphocytes Cai2+ response to Con A significantly decreased on days 1 and 2 after implantation. A significant decrease in T-cell proliferative response to Con A, compared to sterile controls, was found in septic rats on day 2 but not on day 1. These results suggest that Con A-mediated proliferation in T-cells occurs secondarily to a decrease in cellular Ca2+ signalling. The depression in the T-cell proliferative response during sepsis could contribute to a decrease in host's resistance against sepsis.

Topics: Animals; Bacteroides fragilis; Bacteroides Infections; Calcium; Concanavalin A; Disease Models, Animal; Escherichia coli Infections; In Vitro Techniques; Kinetics; Lymphocyte Activation; Male; Rats; Rats, Sprague-Dawley; Sepsis; Signal Transduction; Spleen; T-Lymphocytes

Alterations in T-lymphocyte kinetics and/or activation have been implicated in burn and traumatic injury. This study evaluated concanavalin A (Con A) regulation of both intracellular Ca2+ (Ca2+i) and proliferation in T-lymphocytes harvested from spleens of septic rats. Rats were implanted with fecal pellets containing Escherichia coli (150 colony forming units (CFU)) and Bacteroides fragilis (10(4) CFU). T-cell [Ca2+]i was measured before and after treatment of cells with Con A, using Fura-2 and microfluorophotometry. Splenic lymphocytes were cultured for 72 h with Con A to assess their proliferative response. As compared to sterile-implanted rats, the septic rat T-lymphocytes Ca2+i response to ConA significantly decreased on days 1 and 2 after implantation. A significant decrease in T-cell proliferative response to Con A, compared to sterile controls, was found in septic rats on day 2 but not on day 1. These results suggest that Con A-mediated proliferation in T-cells occurs secondarily to a decrease in cellular Ca2+ signalling. The depression in the T-cell proliferative response during sepsis could contribute to a decrease in host's resistance against sepsis.

Topics: Animals; Calcium; Cell Division; Cells, Cultured; Concanavalin A; Male; Rats; Rats, Sprague-Dawley; Sepsis; Signal Transduction; T-Lymphocytes

Although hemorrhage depresses splenocyte (SPL) functions and increases susceptibility to sepsis, it is not known whether increased tumor necrosis factor (TNF) or prostaglandin (PG) production are responsible for it. To study this, mice (C3H/HeN) were bled to a mean blood pressure of 35 mm Hg, maintained at that pressure for 60 min, resuscitated, and treated with ibuprofen (1.0 mg/kg body weight) or vehicle (saline). Hemorrhage reduced (P less than 0.05) SPL proliferation by 60%, SPL release of interleukin-2 (IL-2) by 47%, interferon-gamma (IFN-gamma) by 67%, TNF by 54%, and interleukin-6 (IL-6) by 46% compared to sham. In addition, splenic macrophage (sM phi) release of interleukin-1 (IL-1) and TNF was decreased by 58 and 67% (P less than 0.05), respectively. However, ibuprofen treatment increased (P less than 0.05) SPL proliferation, lymphokine (IL-2, IFN-gamma, and IL-6) synthesis, and IL-1 release by sM phi compared to hemorrhage alone. Furthermore, ibuprofen enhanced the release of TNF by SPL (+175%, P less than 0.05) and sM phi (+68%) compared to the vehicle group. Ibuprofen also decreased (P = 0.011) the susceptibility to sepsis following hemorrhage. These results indicate that PGs are involved in hemorrhage-induced suppression of cellular immunity and in the increased mortality of such animals following a septic challenge.

Topics: Animals; Blood Pressure; Cells, Cultured; Concanavalin A; Cytokines; Disease Susceptibility; DNA Replication; Hemorrhage; Ibuprofen; Immunity, Cellular; Interferon-gamma; Interleukin-2; Interleukin-6; Lymphocyte Activation; Male; Mice; Mice, Inbred C3H; Sepsis; Spleen; Tumor Necrosis Factor-alpha

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, Surface; B-Lymphocytes; Concanavalin A; Humans; Middle Aged; Mitosis; Multiple Organ Failure; Multiple Trauma; Neutrophils; Phytohemagglutinins; Pokeweed Mitogens; Prospective Studies; Receptors, Interleukin-2; Sepsis; T-Lymphocytes

The effect of hydrocortisone on the number of circulating lymphocytes and their blastogenic response was studied in 20 feedlot lambs given combinations of 3 treatments: hydrocortisone (25 mg/kg of body weight, 4 times a day, IM), feed changes (100% roughage to 90% concentrate over a 6-day period), and oral inoculation of Pasteurella haemolytica biotype T (10(9) to 10(11) bacteria/day via stomach tube) to develop a model for reproduction of septicemic pasteurellosis. Hydrocortisone caused lymphopenia and inhibited the blastogenic response of peripheral blood lymphocytes to phytohemagglutinin and concanavalin A mitogens. A synergistic effect was observed between hydrocortisone injections and feed changes resulting in higher than expected serum hydrocortisone concentrations and lower circulating lymphocyte counts. Seemingly, stress-induced increases in serum hydrocortisone concentrations cause suppression of the immune response of feedlot lambs. The combined effect of feed changes and stress on the immune response of lambs may explain the role of these 2 factors in the pathogenesis of septicemic pasteurellosis.

Topics: Animals; Cattle; Cattle Diseases; Concanavalin A; Disease Models, Animal; Hydrocortisone; Leukocyte Count; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes; Pasteurella Infections; Phytohemagglutinins; Sepsis

Using lectin affinity crossed immunoelectrophoresis with concanavalin A in the first dimension and electroendosmotic elution with sugar in the second dimension, the microheterogeneity of a range of plasma proteins was examined. Of the five chosen proteins, alpha 1-protease inhibitor and caeruloplasmin displayed complex patterns, with more than four components. Alpha 1-Antichymotrypsin was composed of three or four components whilst alpha 1-acid glycoprotein and alpha 2-HS glycoprotein displayed two, three or four components. The number of components seen in these proteins depended on the serum sample origin. In pregnancy and in patients receiving exogenous aestrogen the relative proportions of the components of all five proteins were altered in the direction of less con A binding; however alpha 1-acid glycoprotein and alpha 1-antichymotrypsin showed the greater change. In acute disorders the proportions of protein components of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein were altered towards a higher level of con A binding components. There is no significant alteration in con A binding associated with the chronic inflammatory response to cancer and rheumatoid arthritis. There was a general reduction of con A binding in all five plasma proteins in conditions when there was a high blood aestrogen level. This decreased affinity for con A was independent of the overall effect of the aestrogen on the serum concentration of the plasma protein. These results suggest that the glycosylation of plasma proteins is probably under the same regulatory system.

Topics: Chemical Phenomena; Chemistry; Concanavalin A; Female; Glycoproteins; Humans; Immunoelectrophoresis, Two-Dimensional; Inflammation; Pregnancy; Pregnancy Proteins; Sepsis

The high morbidity after severe thermal insult is believed to be related partially to a resultant decrease in immunocompetence. We tested the ability of phytohemagglutinin (PHA) and Concanavalin (Con A) to stimulate lymphocyte transformation in 17 patients with moderate to severe thermal injury (greater than 25% BSA). The patients acted as their own controls and the per cent change in their mitogen response was measured over time. Eight acutely burned patients who subsequently developed severe sepsis (Group I) had decreased ability (mean, 12% of normal) to proliferate in response to PHA, and six of these died of severe sepsis. The depressed response appeared 4 to 7 days postinjury and predated clinical evidence of sepsis by 2 to 4 days. Cells from four patients who had mild infectious complications (Group II) demonstrated greatly augmented mitogen responses (mean + 243%) approximately 7 to 10 days postinjury. Five burn patients whose clinical course was sepsis free (Group III) exhibited only minimal changes in their mitogen responses (mean +30%). Although the Con A responses of the patients' cells corresponded less to their pathology, Group I patients whose cells exhibited depressed PHA responsiveness also had diminished Con A responses. Group II patients' cells also showed increases in Con A-induced stimulation. Group III patients, who had only slightly augmented PHA responses, had minimal decreases of the Con A-induced lymphocyte transformation. Many severely burned patients develop septicemia as a result of their large wound surfaces. The appearance of decreases in mitogen-induced proliferation, however, appears to characterize those patients who will be unable to handle the septic challenge.

Topics: Adult; Aged; Bacterial Infections; Burns; Concanavalin A; Escherichia coli Infections; Female; Humans; Immunocompetence; Klebsiella Infections; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Prognosis; Pseudomonas Infections; Sepsis; Staphylococcal Infections; T-Lymphocytes; Time Factors