ovalbumin and Shock--Septic

Awara (Astrocaryum vulgare M.) is a palm fruit mainly used in nutrition. We analysed the pulp oil for fatty acid, tocopherol, carotenoid, and phytosterol and we evaluated whether this oil may attenuate inflammation in vivo. In an endotoxic shock model, awara pulp oil treatment decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines. In a pulmonary inflammation model, awara pulp oil treatment reduced eosinophil and lymphocyte numbers recovered into the broncho-alveolar lavages. These results suggest that awara pulp oil administration can efficiently counteract an acute and chronic inflammatory response in vivo that is probably mediated by fatty acids and minor compounds.

Topics: Animals; Anti-Inflammatory Agents; Arecaceae; Carotenoids; Fatty Acids; Lipopolysaccharides; Lung Diseases; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Phytosterols; Plant Oils; Random Allocation; Rats; Shock, Septic; Tocopherols

There is growing evidence that chemokines recruit leukocytes in allergic, inflammatory and immune responses. CC chemokine receptor 4 (CCR4) is implicated as a preferential marker for T helper 2 cells, and the cells selectively respond to CC chemokine ligand 17 (CCL17) and CCL22. We searched for compounds having a profile as a CCR4 antagonist from an in-house library and have previously reported that 3-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}quinazoline-2,4(1H,3H)-dione (named RS-1154) was capable of significantly inhibiting the binding of [(125) I]CCL17 to human CCR4-expressing CHO cells. From further synthesis of its derivatives, we newly focused on 3-(isobutyrylamino)-N-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}benzamide (RS-1269), which showed potency comparable to RS-1154 in inhibiting CCL17-induced migration of DO11.10 mice-derived T helper 2 cells with an IC(50) value of 5.5 nM in vitro. We then investigated the pharmacological effects of RS-1269 on ovalbumin-induced ear swelling and lipopolysaccharide-induced endotoxic shock in mice. The ear thickness was significantly decreased by oral administration of RS-1269 at the dose of 30 mg/kg. Treatment with lipopolysaccharide significantly increased the serum level of tumour necrosis factor-α. Compared with an anti-CCL17 antibody, RS-1269 significantly inhibited the production at the dose of 100 mg/kg. These results raise the possibility that RS-1269 or one of its derivatives has potential to serve as a prototype compound to develop therapeutic agents for atopic dermatitis and inflammatory diseases.

Topics: Administration, Oral; Animals; Benzamides; Chemotaxis, Leukocyte; Ear, External; Edema; Female; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Transgenic; Morpholines; Ovalbumin; Receptors, CCR4; Shock, Septic; T-Lymphocytes, Helper-Inducer; Tumor Necrosis Factor-alpha

IL-33, a member of the IL-1-related cytokines, is considered to be a proallergic cytokine that is especially involved in Th2-type immune responses. Moreover, like IL-1α, IL-33 has been suggested to act as an "alarmin" that amplifies immune responses during tissue injury. In contrast to IL-1, however, the precise roles of IL-33 in those settings are poorly understood. Using IL-1- and IL-33-deficient mice, we found that IL-1, but not IL-33, played a substantial role in induction of T cell-mediated type IV hypersensitivity such as contact and delayed-type hypersensitivity and autoimmune diseases such as experimental autoimmune encephalomyelitis. Most notably, however, IL-33 was important for innate-type mucosal immunity in the lungs and gut. That is, IL-33 was essential for manifestation of T cell-independent protease allergen-induced airway inflammation as well as OVA-induced allergic topical airway inflammation, without affecting acquisition of antigen-specific memory T cells. IL-33 was significantly involved in the development of dextran-induced colitis accompanied by T cell-independent epithelial cell damage, but not in streptozocin-induced diabetes or Con A-induced hepatitis characterized by T cell-mediated apoptotic tissue destruction. In addition, IL-33-deficient mice showed a substantially diminished LPS-induced systemic inflammatory response. These observations indicate that IL-33 is a crucial amplifier of mucosal and systemic innate, rather than acquired, immune responses.

Topics: Adaptive Immunity; Animals; Autoimmunity; Colitis; Immunity, Innate; Immunity, Mucosal; Interleukin-1; Interleukin-33; Interleukins; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Respiratory Hypersensitivity; Shock, Septic

The role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, was tested using a mouse asthma model.. One hundred and four male BALB/c mice were used in this study.. Mice were actively sensitized with an intraperitoneal injection of ovalbumin (OVA) and challenged with repeated nebulization of 1 w/v% OVA. Polyclonal anti-MIF antibody was intraperitoneally injected at 10 mg/kg during the antigen challenge period.. Bronchoalveolar lavage (BAL) was performed 8 h after the last challenge. Airway hyperresponsiveness to inhaled methacholine was measured 24 h after the last challenge.. Antigen challenge to immunized mice induced increase in inflammatory cells and concentration of Th2 cytokines in BAL fluid (BALF), and caused the development of airway hyperresponsiveness. Anti-MIF antibody significantly decreased the numbers of inflammatory cells including macrophages, eosinophils, lymphocytes and neutrophils in BALF from OVA-challenged mice. Prednisolone decreased the numbers of eosinophils, lymphocytes and neutrophils but not macrophages. Anti-MIF antibody reduced airway hyperresponsiveness. Anti-MIF antibody affected neither the cytokine levels in BALF nor the IgE levels in serum.. MIF was involved in the antigen-induced inflammatory cell accumulation in the lung and airway hyperresponsiveness without affecting immune responses.

Topics: Animals; Anti-Inflammatory Agents; Antibodies, Blocking; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Immunoglobulin E; Inflammation; Lipopolysaccharides; Macrophage Migration-Inhibitory Factors; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Plethysmography, Whole Body; Prednisolone; Respiratory Hypersensitivity; Shock, Septic

Intravenous injection of a lipopolysaccharide (LPS) into mice induces a rapid accumulation of platelets in the lung and liver. When degradation of the accumulated platelets occurs, anaphylactoid shock follows rapidly, the severity of the shock paralleling the quantity of platelets accumulated in the lung. Here we examined the contributions made by LPS structure and the complement system to the platelet response to LPS. BALB/c mice were injected with an LPS from Escherichia coli O8, O9, O111, or K-12, or from recombinant mutants of K-12. The O-regions of the O8 and O9 LPSs consist of a mannose homopolysaccharide (MHP), while that of O111 consists of a heteropolysaccharide (not including mannose), and K-12 LPS lacks an O-region. O111 LPS was devoid of the ability to induce the platelet response or shock, while the ability of K-12 LPS was weak. The 2 recombinant LPSs-each having an O-region (from O8 or O9) linked to K-12 LPS-exhibited activities similar to or stronger than those of their original LPSs. Mannose-binding lectin (MBL) complexed with MBL-associated serine proteases (MASPs) bound strongly to LPSs containing MHP and caused C4 activation. Moreover, the abilities of these LPSs to activate the complement system corresponded well with their abilities to induce the platelet response and rapid shock. These results suggest that the structure of the O-antigen region is important for the platelet response to LPS, and that activation of the lectin pathway of the complement system is involved in this response.

Topics: Anaphylaxis; Animals; Blood Platelets; Complement Activation; Complement C4; Complement C5; Endotoxins; Escherichia coli; Histamine; Humans; Injections, Intravenous; Lectins; Lipopolysaccharides; Liver; Lung; Male; Mannose; Mannose-Binding Lectin; Mannose-Binding Protein-Associated Serine Proteases; Mast Cells; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred DBA; O Antigens; Ovalbumin; Pyrilamine; Serine Endopeptidases; Serotonin; Sesquiterpenes; Shock, Septic; Structure-Activity Relationship

In anaphylactic shock, SR 27417, the first member of a newly developed series of PAF (platelet-activating factor) antagonists, inhibited in a dose-dependent manner the lethal effect of antigen (ovalbumin) rechallenge in actively sensitized mice. It protected mice when given i.v. 5 min before ovalbumin challenge (ED50 = 50 micrograms/kg) or when given p.o. 1 h before ovalbumin administration (ED50 = 1.25 mg/kg). After i.v. or oral administration, SR 27417 (2.5 and 10 mg/kg, respectively) greatly improved the survival rate of mice after antigen challenge and had an extremely long duration of action (48 and 30 h, respectively). Similarly, i.v. or oral doses of SR 27417 afforded in mice complete protection against endotoxin-induced lethality (ED50 values were 100 and 150 micrograms/kg, respectively). SR 27417 (1 mg/kg) inhibited endotoxin-induced death in mice with impressive oral or i.v. durations of action of 66 and 110 h, respectively. These results confirm that PAF plays a major role in anaphylactic and endotoxin-induced shock and that SR 27417 may be an effective preventative drug.

Topics: Anaphylaxis; Animals; Azepines; Dose-Response Relationship, Drug; Endotoxins; Escherichia coli; Male; Mice; Mice, Inbred Strains; Ovalbumin; Platelet Activating Factor; Shock, Septic; Thiazoles; Triazoles

Topics: Anaphylaxis; Animals; Antigens; Azepines; Disease Models, Animal; Endotoxins; Escherichia coli; Guinea Pigs; Lung Diseases; Ovalbumin; Platelet Activating Factor; Pyrilamine; Shock, Septic; Triazines; Triazoles

Topics: Anaphylaxis; Animals; Antigens; Benzyl Compounds; Chromatography, Ion Exchange; Dose-Response Relationship, Drug; Epinephrine; Ethylenediamines; Guinea Pigs; Histamine; Histamine H1 Antagonists; Norepinephrine; Ovalbumin; Pyridines; Shock, Septic; Toxins, Biological

Oxisuran, 2-([methylsulfinyl]acetyl)pyridine, has previously been shown to selectively suppress cell-mediated immunity, as measured by prolongation of allograft survival, without inhibition of humoral immunity. In the present investigation, the influence of this compound on lymphoid cell transfer of delayed hypersensitivity was studied. In actively sensitized animals, including endotoxin-sensitized mice and rabbits, ovalbumin-, dinitrochlorobenzene-, and dinitrofluorobenzene-sensitive guinea pigs, or tuberculin-sensitive rats, daily treatment during the interval just preceding the elicitation and expression of the hypersensitivity was most inhibitory. In both endotoxin-sensitive mice and ovalbumin-sensitive guinea pigs, treatment of the sensitized cell donor just prior to lymphoid cell harvest and transfer resulted in inhibition of the expression of the hypersensitivity in untreated recipients. Approximately 10(4) fewer specifically sensitized lymphoid cells, but not fewer viable cells, were present in passively transferred cell preparations. In contrast, treatment of the lymphoid cell recipient in the same experimental model did not influence the expression of the transferred hypersensitivity. The results suggest that oxisuran may influence an as yet undefined event prior to the expression of a cell-mediated hypersensitivity response in sensitized animals.

Topics: Animals; Antibody-Producing Cells; Antigens; Antigens, Bacterial; Endotoxins; Female; Guinea Pigs; Hemolytic Plaque Technique; Hypersensitivity, Delayed; Immunity, Cellular; Immunization, Passive; Lymphocytes; Mice; Nitrobenzenes; Ovalbumin; Pyridines; Rabbits; Rats; Salmonella; Shock, Septic; Skin Tests; Spleen

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Carotid Arteries; Guanidines; Guinea Pigs; Heparin; Histamine; Jugular Veins; Ovalbumin; Shock, Septic; Toxins, Biological

Topics: Animals; Dextrans; Ovalbumin; Quaternary Ammonium Compounds; Rats; Shock, Septic