Involvement of leukotrienes in allergic pleurisy in actively sensitized rats: inhibition by the lipoxygenase inhibitor T-0757 of the increase in vascular permeability and leukotriene E4 production.
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.
Kikuchi
M
M
Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co. Ltd., Saitama, Japan.
Tsuzurahara
K
K
Suzuki
T
T
Yato
N
N
Naito
K
K
D000577:Amides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005122:Exudates and Transudates / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D017999:Leukotriene E4 / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010047:Ovalbumin / Q000633:toxicity; D010994:Pleura / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000577:Amides; D016861:Cyclooxygenase Inhibitors; D006634:Histamine H1 Antagonists; D016859:Lipoxygenase Inhibitors; C097368:T 0757; D003533:Cyproheptadine; D017999:Leukotriene E4; D006632:Histamine; D010047:Ovalbumin; D007213:Indomethacin