leukotriene-e4 and Pleurisy

The relative contributions of inflammatory mediators to the increase in vascular permeability in antigen-induced pleurisy were examined in rats actively sensitized with ovalbumin. The effects of various inhibitors were assessed on the exudate volume and plasma exudation rate in the pleural cavity. Two peaks were observed in plasma exudation rate at 0.5 and 3 h after antigen challenge. At 0.5 h, there was a marked decrease in the histamine content of the pleural cells and also a sharp increase in the LTE4 level in the exudate, which was inhibited dose-dependently by the lipoxygenase inhibitor T-0757. Indomethacin and cyproheptadine both depressed exudate volume and exudation rate, whereas T-0757 only reduced the exudation rate. At 3 h, a substantial LTE4 concentration was still detected in the exudate, and the exudation rate was depressed by T-0757 and indomethacin, but not by cyproheptadine. These results suggest that histamine is involved mainly in the early phase, and leukotrienes predominantly contribute to the later phase of exudation. Prostaglandins appear to be involved in both phases. Allergic pleurisy of rats, therefore, may be a suitable model to examine the roles of these inflammatory mediators.

Topics: Amides; Animals; Capillary Permeability; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Cyproheptadine; Dose-Response Relationship, Drug; Exudates and Transudates; Histamine; Histamine H1 Antagonists; Indomethacin; Leukotriene E4; Lipoxygenase Inhibitors; Male; Ovalbumin; Pleura; Pleurisy; Rats; Rats, Wistar

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclosporins; Dinoprostone; Exudates and Transudates; Leukotriene E4; Male; Organ Size; Phospholipases A; Pleurisy; Rats; Rats, Inbred Strains; SRS-A; Thymus Gland

Rat IgE pleurisy was induced by the injection of di-nitrophenol-conjugated bovine serum albumin (DNP-BSA) 48 hours after the intrapleural injection of rat anti-DNP-IgE serum. IgG-BSA complex pleurisy was also induced by the intrapleural injection of IgG-BSA complexes produced at the optimum ratio in vitro. Plasma exudation was markedly increased in the first 20 minutes, but not observed thereafter, in IgE pleurisy, whereas marked plasma exudation in the first 20 minutes was followed by weak exudation at three and five hours in IgG-BSA complex pleurisy. Leukotrienes (LTs) E4 (100 ng/rat), D4 (32) and B4 (16) were detected on HPLC in the pleural exudate in the first 20 minutes of IgG-BSA complex pleurisy, but less (9 ng/rat) LTE4 alone was detected in the five-hour exudate. The first 20-minute pleural exudate contained 13 ng/rat of LTE4 in IgE pleurisy. The plasma was completely inhibited by simultaneous treatment of rats with pyrilamine (2.5 mg/kg, i.p.) and methysergide (3 mg/kg, i.p.), as it was in compound 48/80-induced pleurisy. In IgG-BSA complex pleurisy, 90% of the pleural exudate for the first 20 minutes was inhibited by the same treatment, and the rest was completely suppressed by simultaneous treatment with an intrapleural injection of AA-1777, a selective 5-lipoxygenase inhibitor. AA-1777 alone did not reduce the plasma exudation significantly. The 5-lipoxygenase inhibitor was also very effective in reducing the migrating numbers of polymorphonuclear and mononuclear leukocytes to half, without affecting the eosinophils of mast cells.

Topics: Animals; Antigen-Antibody Complex; Benzoquinones; Chemotaxis, Leukocyte; Chromatography, High Pressure Liquid; Disease Models, Animal; Exudates and Transudates; Immunoglobulin E; Immunoglobulin G; Leukotriene B4; Leukotriene E4; Lipoxygenase Inhibitors; Methysergide; Pleurisy; Pyrilamine; Quinones; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Serotonin; Respiratory Hypersensitivity; SRS-A