Grcadian rhythm of interleukin-1 production of monocytes and the influence of endogenous and exogenous glucocorticoids in man

Abstract

We found a dose-dependent inhibition of spontaneous and LPS-induced IL-1 production of isolated human monocytes by methylprednisolone (MP) in vitro. Kinetic studies of spontaneous and LPS-induced IL-1 production of isolated monocytes of 10 normal individuals showed a synchronous circadian rhythm, with its maximum at 4:00 p.m. and its minimum at 4:00 a.m., which is most probably independent of the physiological circadian rhythm of cortisol levels because the IL-1 production was of the same value at the times of maximum and minimum cortisol levels. In contrast, in a patient with hypercortisolism and a preserved circadian rhythm of cortisol levels, we found the minimum of IL-1 production at 4:00 p.m., 8 hours after the maximum cortisol level was reached. Furthermore, in 7 patients with sarcoidosis both spontaneous and LPS-induced IL-1 production of isolated monocytes were significantly decreased 8 hours after the first injection of MP (1 mg/kg bw i.v.) compared to the values before MP administration. Our findings suggest a physiological circadian rhythm of spontaneous and LPS-induced IL-1 production of monocytes, independent of physiological cortisol levels, whereas unphysiological amounts of endogenous and exogenous glucocorticoids cause a substantial inhibition of IL-1 production with a latency time of 8 hours.