DIURNAL RHYTHMS OF PRO-INFLAMMATORY CYTOKINES - REGULATION BY PLASMA-CORTISOL AND THERAPEUTIC IMPLICATIONS

Clinical features of certain immune-inflammatory disorders such as rhe umatoid arthritis and asthma exhibit diurnal fluctuation, which could be related to diurnal rhythmicity of proinflammatory cytokine producti on. To investigate the latter, the authors performed measurements of l ipopolysaccharide (LPS)-stimulated whole blood, interferon gamma (IFN- gamma), tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and IL-12 production in 13 healthy volunteers over 24 h, These cytoki nes exhibited distinct diurnal rhythms that peaked in the early mornin g and were inversely related to the rhythm of plasma cortisol, Elevati on of plasma cortisol within the physiological range by administration of cortisone acetate, 25 mg at 21.00, markedly suppressed IFN-gamma, TNF-alpha, IL-1 and IL-12 production, but not the later early morning rise of endogenous plasma cortisol, Suppression of cytokine production was temporally dissociated from changes in numbers of circulating mon onuclear cells. Regulation of pro-inflammatory cytokine production by plasma cortisol has potential therapeutic implications. In contrast to standard schedules, a small, late evening, dose of glucocorticoid to suppress the diurnal increase in pro-inflammatory cytokine production could alleviate early morning inflammatory symptoms and minimize side- effects. (C) 1998 Academic Press Limited.