Salicylates and the adrenal cortex.

The salicylates have been used in the symptomatic treatment of rheumatic disorders for over 50 years. They are capable of producing a striking change in the clinical picture of acute rheumatic fever and possess a smaller, but still definite, effect in rheumatoid arthritis. Their value as suppressive drugs appears to be concerned with alleviating the symptoms produced by the inflammatory processes which form a major part of the reaction of the body in rheumatic disease. The mechanism of this antiinflammatory action of salicylates is particularly obscure. In recent years, cortisone and related hormones have also been widely used as antirheumatic drugs. Their clinical effects in rheumatism are very similar to those of salicylates and it has been suggested that salicylate therapy is essentially corticosteroid therapy. More sophisticated versions of this statement have included mechanisms such as stimulation of the anterior pituitary and adrenal cortex and an accelerated rate of removal of circulating corticosteroids during salicylate treatment (Hailman, 1952; Roskam, 1956; Done, Ely, and Kelley, 1958). The purpose of the present article is to show that the available evidence, if examined critically, fails to provide convincing proof of the validity of the hypothesis that the therapeutic actions of salicylates in rheumatism are mediated by the adrenal cortex or its hormones. If salicylates act through the adrenal cortex, they may do so in one or more of three ways: