Katler E, Weissmann G
Inflammation. 1977 Dec;2(4):295-307. doi: 10.1007/BF00921009.
The ability of adrenal corticosteroids to both both suppress inflammation and compromise host defenses has been well documented. Recently, a series of in vitro and in vivo experiments, based on our new knowledge of the cell biology of inflammation and the biochemistry of the phagocytic cell itself, has provided new insights into the mechanism of steroid action in the inflammatory process. Evidence is presented that pharmacologic doses of steroids are capable of inhibiting each of the steps in phagocytic-micro-organism interaction: chemotaxis, recognition and opsonization, phagocytosis, membrane fusion, and degranulation. In addition, steroid alteration of the postphagocytic superoxide production, hydrogen peroxide generation, and prostaglandin and thromboxane synthesis is described. The antiinflammatory effects of aspirin and indomethacin can be explained almost entirely by virtue of their ability to inhibit cyclooxygenase, this preventing the transformation of arachidonic acid to both prostaglandins and thromboxanes. The cortisol-induced inhibition of endoperoxides, prostaglandins, and thromboxanes (at a site proximal to the release of arachidonic acid) may well explain those antiinflammatory actions that cortisone shares with aspirin. However, patients treated with nonsteroidal antiinflammatory agents effectively combat infections. In contrast, corticosteroids have more profound effects, as can be seen by the inhibition of superoxide production, with the subsequent decrease in hydrogen peroxide generation and the diminution in release of the antibacterial lysosomal hydrolases within the phagocytic vacuole. Thus, corticosteroids interfere with the killing of microorganisms. This new understanding of the pharmacologic action of cortisol on phagocytic cells explains, we believe, how glucocorticoids alleviate inflammation while, at the same time, they permit multiplication of the offending microorganism within the phagocyte.
肾上腺皮质类固醇抑制炎症和损害宿主防御的能力已有充分文献记载。最近，基于我们对炎症细胞生物学和吞噬细胞自身生物化学的新知识，一系列体外和体内实验为类固醇在炎症过程中的作用机制提供了新的见解。有证据表明，药理剂量的类固醇能够抑制吞噬细胞与微生物相互作用的每一个步骤：趋化作用、识别与调理作用、吞噬作用、膜融合和脱颗粒。此外，还描述了类固醇对吞噬后超氧化物产生、过氧化氢生成以及前列腺素和血栓素合成的改变。阿司匹林和吲哚美辛的抗炎作用几乎完全可以通过它们抑制环氧化酶的能力来解释，这阻止了花生四烯酸转化为前列腺素和血栓素。皮质醇对内过氧化物、前列腺素和血栓素的诱导抑制（在花生四烯酸释放的近端位点）很可能解释了可的松与阿司匹林共有的那些抗炎作用。然而，用非甾体抗炎药治疗的患者能有效对抗感染。相比之下，皮质类固醇有更深远的影响，从超氧化物产生的抑制可以看出，随后过氧化氢生成减少，吞噬泡内抗菌溶酶体水解酶的释放减少。因此，皮质类固醇会干扰微生物的杀灭。我们认为，对皮质醇对吞噬细胞药理作用的这一新认识解释了糖皮质激素如何减轻炎症，同时又允许有害微生物在吞噬细胞内繁殖。
