STEROID-METABOLISM AND IMMUNITY - THERAPEUTIC IMPLICATIONS

The glucocorticoids are generally regarded as immunosuppressants. In r eality they are immunoregulatory, with both positive and negative effe cts on the immune system. The effects of glucocorticoids in any given tissue cannot easily be related to the early morning plasma cortisol l evel. The diurnal rhythm, which in normal people results in occupation of the glucocorticoid receptors in T lymphocytes for about half the 2 4-hour cycle, is also important. Moreover, the effects within each tis sue depend upon the metabolism, both systemically and within each tiss ue, of the glucocorticoids themselves and of other steroids derived fr om dehydroepiandrosterone sulphate that have antiglucocorticoid proper ties. These points highlight numerous potential targets for novel ther apies, including: (i) the regulation of the glucocorticoid/dehydroepia ndrosterone balance; (ii) regulation of the diurnal rhythm; (iii) deve lopment of inhibitors of enzymes that metabolise glucocorticoids or de hydroepiandrosterone in different tissues; and (iv) use of novel combi nations of glucocorticoid and antiglucocorticoid (dehydroepiandrostero ne) metabolites that have properties unlike those of either steroid us ed alone.