Mechanisms for anti-inflammatory actions of glucocorticoid

采用几种气囊型炎症模型研究糖皮质激素的抗炎作用机制。(1)将1.6%酵母聚糖溶于0.8% CMC-Na溶液注入气囊内，1小时后气囊液中前列腺素E_2（PGE_2）和肽-白三烯（LTs）水平升高。在注射酵母多糖前3小时或注射地塞米松后1小时，囊液中的PGE_2和肽-LTs水平均降低。虽然地塞米松的这些作用弱于AA 861，地塞米松对0.5 ~ 1小时血管通透性反应的抑制作用强于AA 861。(2)放线菌素D可抑制脂多糖诱导的中性粒细胞聚集和4小时时囊液中趋化活性的增加，但AA 861不能抑制。地塞米松降低了LPS注射后4小时的趋化活性和中性粒细胞浸润的囊液中的数量。(3)地塞米松预处理抑制酵母多糖激活的血清诱导的中性粒细胞浸润在第一个1小时内，而不减少在袋液中的趋化活性。这些结果提示地塞米松抑制血管通透性反应和中性粒细胞浸润的机制不同于抑制磷脂酶A_2。地塞米松抑制中性粒细胞浸润归因于抑制蛋白样趋化因子的产生以及中性粒细胞和/或血管内皮细胞对趋化因子的反应。因此，糖皮质激素对磷脂酶A_2的抑制作用不是其抗炎作用的主要机制。

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.