Zabel P, Horst H J, Kreiker C, Schlaak M
Medizinische Klinik, Forschungsinstitut Borstel.
Klin Wochenschr. 1990 Dec 17;68(24):1217-21. doi: 10.1007/BF01796513.
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.
我们发现，在体外，甲基强的松龙（MP）对分离出的人单核细胞自发产生及脂多糖（LPS）诱导产生白细胞介素-1（IL-1）具有剂量依赖性抑制作用。对10名正常个体分离出的单核细胞自发产生及LPS诱导产生IL-1的动力学研究显示，其具有同步的昼夜节律，在下午4点达到峰值，凌晨4点降至最低，这很可能独立于皮质醇水平的生理昼夜节律，因为在皮质醇水平最高和最低时，IL-1的产生量相同。相比之下，在一名皮质醇增多症患者中，其皮质醇水平的昼夜节律保持正常，我们发现IL-1产生的最低值出现在下午4点，此时距离皮质醇水平达到最高值已有8小时。此外，在7名结节病患者中，首次静脉注射MP（1 mg/kg体重）8小时后，分离出的单核细胞自发产生及LPS诱导产生IL-1的水平均较MP给药前显著降低。我们的研究结果表明，单核细胞自发产生及LPS诱导产生IL-1具有生理昼夜节律，独立于生理皮质醇水平，而内源性和外源性糖皮质激素的非生理量会导致IL-1产生受到显著抑制，且存在8小时的延迟时间。
