METABOLITES OF HYDROCORTISONE AND CORTISONE IN SYNOVIAL FLUID IN RHEUMATOID ARTHRITIS*

Abstract

Detailed chromatographic analyses of extracts of synovial fluid were made at two time intervals after the intra-articular injection of 100 mg of free hydrocortisone and of cortisone in subjects with rheumatoid arthritis. Several metabolites, of both greater and lesser polarity than the injected steroids were found, ranging from possible C21O6 corticosteroids to C19O3 and C19O2 17-ketosteroids. [DELTA] 4-Androstene-11[beta]-ol-3, 17,-dione was identified as a metabolite of hydrocortisone. Thus the ability of rheumatoid synovial tissue to metabolize hydrocortisone and cortisone in vivo was confirmed. Substantial amounts of hydrocortisone were identified after the injection of cortisone. The pattern of metabolites of the two hormones were strikingly different. Since cortisone does not have anti-inflammatory activity in the knee, the local effectiveness of hydrocortisone may therefore involve the production of a specific metabolite. When the extracted synovial fluid was incubated first with [beta]-glucuronidase and then with papain, and each incubation was followed by solvent extraction, further yields of steroids were obtained. Some of these were the same as those in the first extract, while others were liberated only after enzyme treatment. The largest fraction liberated by papain consisted of 17-ketosteroids amounting to 35% of the total obtained.