Regulation of 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 in Rheumatoid Arthritis

Objective: The sequential activities of the 11β-hydroxysteroid dehydrogenase enzymes type 1 and 2 have not been investigated so far in patients suffering from rheumatoid arthritis before and after starting treatment though the enzymes balancing cortisol and cortisone levels are involved in regulating various inflammatory diseases. Methods: In a retrospective study, a panel of 41 urinary steroid metabolites has been analysed in a group of 18 patients with active rheumatoid arthritis (RA) as they were brought under control with disease modifying drugs. Results: No major changes were found in a variety of androgen, oestrogen and progesterone metabolites, however the ratio of THF + 5αTHF/THE as an index of 11β-HSD1 oxidative activity demonstrated down-regulation with modification correlating significantly with change in acute phase reactants as the disease came under control. These findings were supported by a tendency of a reduced ratio of F/E, an index of 11β-HSD2 oxidative activity, resulting in a significant correlation of the two ratios (p < 0.001). This parallelism of the two enzymes with functions of clinical laboratory parameters during drug-induced improvement of the disease is novel. Conclusions: Urinary steroid metabolites, which alter with disease activity, may provide further insight into the mechanisms by which stress can modify arthritis through hormones.