Steroid metabolism and immunity: therapeutic implications

The glucocorticoids are generally regarded as immunosuppressants. In reality they are immunoregulatory, with both positive and negative effects on the immune system. The effects of glucocorticoids in any given tissue cannot easily be related to the early morning plasma cortisol level. The diurnal rhythm, which in normal people results in occupation of the glucocorticoid receptors in T lymphocytes for about half the 24-hour cycle, is also important. Moreover, the effects within each tissue depend upon the metabolism, both systemically and within each tissue, of the glucocorticoids themselves and of other steroids derived from dehydroepiandrosterone sulphate that have antiglucocorticoid properties. These points highlight numerous potential targets for novel therapies, including: the regulation of the glucocorticoid/dehydroepiandrosterone balance;regulation of the diurnal rhythm;development of inhibitors of enzymes that metabolise glucocorticoids or dehydroepiandrosterone in different tissues; anduse of novel combinations of glucocorticoid and antiglucocorticoid (dehydroepiandrosterone) metabolites that have properties unlike those of either steroid used alone.