Mechanisms for anti-inflammatory actions of glucocorticoid

Research Project

Project/Area Number	63480460
Research Category	Grant-in-Aid for General Scientific Research (B)
Allocation Type	Single-year Grants
Research Field	Biological pharmacy
Research Institution	TOHOKU UNIVERSITY
Principal Investigator	OHUCHI Kazuo (1989) Tohoku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20006357) 鶴藤丞 (1988) 東北大学, 薬学部, 教授 (40012596)
Co-Investigator(Kenkyū-buntansha)	WADA Yumiko Tohoku University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 教務職員 (70167469) HIRASAWA Noriyasu Tohoku University, Faculty of Pharmaceutical Sciences, Assit. Prof., 薬学部, 助手 (80181155) WATANABE Masako Tohoku University, Faculty of Pharmaceutical Sciences, Assit. Prof., 薬学部, 助手 (90182948) 大内和雄東北大学, 薬学部, 助教授 (20006357)
Project Period (FY)	1988 – 1989
Project Status	Completed (Fiscal Year 1989)
Budget Amount *help	¥5,300,000 (Direct Cost: ¥5,300,000) Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000) Fiscal Year 1988: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywords	Glucocorticoid / Vascular permeability / Neutrophil infiltration / Peptide-leukotriene / Chemotactic factor / 抗炎症薬 / 空気嚢型炎症モデル / ザイモサン炎症 / プロスタグランジンロイコトリエン / 血管透過性反応
Research Abstract	Mechanisms for the anti-inflammatory actions of glucocorticoid were studied using several air pouch type inflammation models. (1) Injection of 1.6 %$(w/v) zymosan in 0.8 % (w/v) CMC-Na solution into the air pouch induced increases in the levels of prostaglandin E_2 (PGE_2) and peptide-leukotrienes (LTs) in the pouch fluid at 1 hr. Administration of a 5-lipoxygenase inhibitor, AA861, at time 0 or dexamethasone 3 hr before the zymosan injection reduced both PGE_2 levels and peptide-LTs levels in the pouch fluid at 1 hr. Although these effects of dexamethasone were weaker than those of AA861, the inhibitory effect of dexamethasone on the vascular permeability response during the period from 0.5 to 1 hr was stronger than that of AA861. (2) Lipopolysaccharide-induced increases in neutrophil accumulation and chemotactic activity in the pouch fluid at 4 hr were inhibited by actinomycin D but not by AA861. Dexamethasone reduced the chemotactic activity and the number of neutrophils infiltrated in the pouch fluid 4 hr after the LPS injection. (3) Pretreatment of dexamethasone inhibited zymosan-activated serum-induced neutrophil infiltration during the first 1 hr without reducing the chemotactic activity in the pouch fluid. These results suggest that dexamethasone inhibits vascular permeability response and neutrophil infiltration by another mechanism than phospholipase A_2 inhibition. Inhibition of neutrophil infiltration by dexamethasone is ascribed to the inhibition of both the production of protein-like chemotactic factor and the responses of neutrophil and/or vascular endothelial cells to chemotactic factors. In conclusion, the inhibitory action of glucocorticoid on phospholipase A_2 is not the main mechanism for anti-inflammatory effects of glucocorticoid.