Steroids, aspirin, and inflammation

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.