Abstract
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.
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References
Dahlen SE, Hedqvist P, Hammarstrom S, Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature 1980;288:484–6.
Hedqvist P, Dahlen SE, Bjork J. Pulmonary and vascular actions of leukotrienes. Adv Prostag Thrombox Leukotr Res 1982;9:187–200.
Thien FCK, Walters EH. Eicosanoids and asthma: update. Prostagland Leukotr Essen Fatty Acids 1995;52:271–88.
Creticos PS, Peters SP, Adkinson NF, Naclerio RM, Hayes EC, Norman PS, et al. Peptide leukotriene release after antigen challenge in patients sensitive to ragweed. New Engl J Med 1984;310:1626–30.
Talbot SF, Arkins PC, Goetzl EJ, Zwiman B. Accumulation of leukotriene C4 and histamine in human allergic skin reactions. J Clin Invest 1985;76:650–6.
Salmon JA, Garland LG. Leukotriene antagonists and inhibitors of leukotriene biosynthesis as potential therapeutic agents. Prog Drug Res 1991;37:9–90.
Taniguchi Y, Tamura G, Honma M, Aizawa T, Maruyama N, Shirato K, et al. The effect of an oral leukotriene antagonist, ONO-1078, on allergen-induced immediate bronchoconstriction in asthmatic subjects. J Aller Clin Immunol 1993;92:507–12.
Israel E, Cohn J, Dube L, Drazen J and the Zileuton Study Group. Effects of Zileuton treatment on chronic stable asthma; results of a 13-week double-blind placebo controlled trial. J Aller Clin Immunol 1994;93:295.
Zuany-Amorim C, Cordeiro RSB, Vargaftig BB. Involvement of leukotrienes in allergic inflammation in mice. Eur J Pharmacol 1994;257:211–6.
Marcia CRL, Marco AM, Sandra ACP, Patricia MRS, Renato SBC, Vargaftig BB. Effect of azelastine on platelet-activating factor and antigen-induced pleurisy in rats. Eur J Pharmacol 1988;197:201–7.
Hagiwara M, Mikami T, Iwamura S, Miyazawa K, Kobayashi M, Miyasawa K. Effects of TZI-41127, a novel selective 5-lipoxygenase inhibitor, on A-23187-induced pleurisy in rats. Eur J Pharmacol 1991;199:69–75.
Ohuchi K, Takahashi C, Watanabe M, Hirasawa N, Suzuki Y, Kudo M. Metabolism of leukotriene C4, D4 and E4 in allergic inflammation in rats. Clin Lab Immunol 1988;27:171–8.
Tanaka K, Ueno A, Katori M. Roles of leukotriene in two rat allergic inflammatory models; IgE-mediated and IgG-antigen complex-induced pleurisies. Prostaglandins 1986;31:1099–116.
Kikuchi M, Hashimura Y, Tsuzurahara K, Nagasawa M, Inoue H, Taniguchi T, et al. 4-Acylaminophenol derivatives as novel lipoxygenase inhibitors: synthesis and inhibitory effect on 5-lipoxygenase and leukotriene B4 production. Biol Pharm Bull 1994;17:1038–46.
Kikuchi M, Ishikawa S, Tsuzarahara K. Inhibitory effect of 4-acylaminophenol derivatives (T-0799 and T-0757), novel lipoxygenase inhibitors, on arachidonic acid-induced infiltration of polymorphonuclear leukocytes in rat skin. Jpn J Pharmacol 1994;66:363–8.
Kikuchi M, Tsuzurahara K, Naito K. Involvement of leukotriene B4 in zymosan-induced rat pleurisy: inhibition of leukocyte infiltration by the 5-lipoxygenase inhibitor T-0757. Biol Pharm Bull 1995;18:1302–4.
Joris I, Majno G, Corey EJ, Lewis RA. The mechanism of vascular leakage induced by leukotriene E4. Am J Pathol 1987;126:19–24.
Irman-Florjanc T, Erjavec F. Histamine tele-methylhistamine ratios in rat blood as a function of time after i.v. injection of compound 48/80 or histamine. Agents Actions 1992;SCI:C394-7.
Blazso G, Gabor M. Anti-oedematous action of some H1-receptor antagonists. Agents Actions 1994;42:13–8.
Ohuchi K, Yoshino S, Kanaoka K, Tsurufuji S, Levine L. A possible role of arachidonate metabolism in allergic air pouch inflammation in rats. Int Arch Allergy Appl Immunol 1982;68:326–31.
Raud J, Dahlen SE, Sydbom A, Lindbom L, Hedqvist P. Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: Apparent correlation with in vivo modulation of mediator release. Proc Natl Acad Sci USA 1988;85:2315–9.
Peck MJ, Piper PJ, Williams TJ. The effect of leukotriene C4 and D4 on the microvasculature of guinea-pig skin. Prostaglandins 1981;21:315–21.
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Kikuchi, M., Tsuzurahara, K., Suzuki, T. et al. 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. Inflamm Res 45, 192–197 (1996). https://doi.org/10.1007/BF02285160
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DOI: https://doi.org/10.1007/BF02285160