Comparison of anti-inflammatory activities between recombinant human lipocortin and glucocorticoid.

脂皮质蛋白是一种介导糖皮质激素抗炎作用的抗炎蛋白。在这项研究中，我们使用由Biogen研究公司（lipocortin-Biogen）或Toray工业公司（lipocortin- Toray）生物技术合成的人脂皮质素，目的是确定脂皮质素的抗炎活性是否与糖皮质激素相当。(1)脂皮质素-生物原抑制tpa诱导的花生四烯酸标记巨噬细胞放射性释放呈剂量依赖性，但其作用远弱于地塞米松。(2)在高岭土诱导的气袋型炎症模型中，脂皮质素- biogen在注射高岭土后20 min内，虽然PGE_2水平呈剂量依赖性降低，但在0 ~ 20 min内未能抑制血管通透性的增加。(3)在酶多糖诱导的气袋型炎症模型中，脂皮质素- toray在注射酶多糖60 min后，既没有降低气袋液中PGE_2水平，也没有在30 ~ 60 min期间增加血管通透性。另一方面，地塞米松，一种合成的糖皮质激素，对这两种反应都有有效且剂量依赖性的抑制作用。(4)脂皮质素-东丽对组胺和PGE_2联合注射小鼠足垫水肿无抑制作用，而地塞米松和另一种合成糖皮质激素倍他米松对足垫水肿有明显的抑制作用，且呈剂量依赖性。结论：重组人脂皮质素无明显抗炎活性。糖皮质激素的抗炎活性不能归因于脂皮质素的作用。

Lipocortin is reported as an anti-inflammatory protein which mediates anti-inflammatory actions of glucocorticoids. In this investigation, using human lipocortin synthesized biotechnologically by Biogen Research Co. (lipocortin-Biogen) or by Toray Industries Inc. (Lipocortin-Toray), we aimed to determine whether anti-inflammatory activities of lipocortin are comparable to those of glucocorticoids.(1) Lipocortin-Biogen inhibited TPA-induced release of radioactivity from [^3H] arachidonic acid-labeled macrophages in a dosedependent manner, but the effect was much weaker than that of dexamethasone.(2) In kaoline-induced air pouch type inflammation model, lipocortin-Biogen failed to inhibit vascular permeability increase during the period of 0 - 20 min, although PGE_2 level in the pouch fluid 20 min after the injection of kaolin was decreased dose-dependently.(3) In zymosan-induced air pouch type inflammation model, lipocortin-Toray reduced neither PGE_2 level in the pouch fluid 60 min after the injection of zymosan, nor vascular permeability increase during the period of 30 - 60 min. On the other hand, dexamethasone, a synthesized glucocorticoid, inhibited both responses potently and dose-dependently.(4) Lipocortin-Toray did not inhibit footpad edema induced by co-injection of histamine and PGE_2 in mice although dexamethasone and another synthesized glucocorticoid, betamethasone, inhibited it potently and dose-dependently.In conclusion, recombinant human lipocortin showed no significant anti-inflammatory activity. The anti-inflammatory activity of glucocorticoids can not be ascribed to the action of lipocortin.