A circadian study of corticosteroid suppression of delayed hypersensitivity

Abstract

Rats were given a single injection of methyl prednisolone or diluent at one of six different clock times, four hours apart. Simultaneously, a delayed hypersensitivity response to oxazolone was initiated and quantitated at 24 h intervals for 72 h. In the non-medicated rats the magnitude of the immune response was seen to depend on the initial timing of the oxazolone challenge. Plasma levels of endogenous 11-hydroxycorticosteroids were high at 22:00 h (the onset of darkness) and 02:00 h relative to the other timepoints of the 12:12 light—dark cycle. The immune response following challenge at these times was also lower to the extent that challenge at 22:00 h evoked a response which was sustained at only one third the level of a challenge at 10:00 h. Immunosuppression was evident at 24 h in the corticosteroid-treated rats but was shown to persist to 48 h only in the group treated and challenged at 02:00 h. It is suggested that drug induced suppression of endogenous corticosteroid production, which is greater at some times than at others, is relevant to the development of the response following the initial pharmacological immunosuppression by synthetic corticosteroid. Other influences on immune responses, and on the availability and activity of drugs, vary on a circadian basis. The effectiveness of drugs acting on the immune process may be increased, or the toxicity decreased, by modification of timing. This study is an initial step in the evaluation of timing being important in the clinical pharmacology of immunosuppressants.