Metyrapone: a possible tool in investigating the role of endogenous corticosteroids in inflammation

Despite much early work on corticosteroid levels in the blood and urine of patients with rheumatic diseases, little strong evidence is available concerning the role of endogenous corticosteroids in inflammation. Nevertheless, the modulating role of adrenal corticosteroids in inflammation seems to be taken for granted even though the small amount of evidence in laboratory animals is, in some cases, contradictory. In the light of the immunological aetiology of some chronic inflammatory diseases and the immunosuppressive properties of corticosteroids, investigations into the role of endogenous corticosteroids in these conditions seem particularly worthwhile. Adrenalectomy has been used widely in studies on the physiological roles of adrenal corticosteroids but the operation requires care to avoid mortality. The adrenal corticosteroid synthesis inhibitor, metyrapone, could be used quite profitably in such investigations. However, it has been shown to exert differential effects on prostaglandin (PG) production in uterine tissue and may produce non-selective antagonism of the actions of PGs. Because PGs are probably involved in inflammation, care should be exercised in the doses of metyrapone used in any studies on inflammatory models to avoid interactions with the PG system.