Petrovsky N, McNair P, Harrison L C
Walter and Eliza Hall Institute, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Cytokine. 1998 Apr;10(4):307-12. doi: 10.1006/cyto.1997.0289.
Clinical features of certain immuno-inflammatory disorders such as rheumatoid arthritis and asthma exhibit diurnal fluctuation, which could be related to diurnal rhythmicity of pro-inflammatory cytokine production. To investigate the latter, the authors performed measurements of lipopolysaccharide (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 cytokines exhibited distinct diurnal rhythms that peaked in the early morning and were inversely related to the rhythm of plasma cortisol. Elevation 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 mononuclear 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.
某些免疫炎症性疾病（如类风湿性关节炎和哮喘）的临床特征呈现昼夜波动，这可能与促炎细胞因子产生的昼夜节律有关。为了研究后者，作者对13名健康志愿者在24小时内脂多糖（LPS）刺激的全血、干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）、白细胞介素1（IL-1）和IL-12的产生进行了测量。这些细胞因子呈现出明显的昼夜节律，在清晨达到峰值，并且与血浆皮质醇的节律呈负相关。在21:00给予25毫克醋酸可的松使血浆皮质醇在生理范围内升高，显著抑制了IFN-γ、TNF-α、IL-1和IL-12的产生，但并未抑制内源性血浆皮质醇在清晨稍后的升高。细胞因子产生的抑制与循环单核细胞数量的变化在时间上是分离的。血浆皮质醇对促炎细胞因子产生的调节具有潜在的治疗意义。与标准给药方案不同 的是，在傍晚小剂量使用糖皮质激素来抑制促炎细胞因子产生的昼夜增加，可能会减轻清晨的炎症症状并使副作用最小化。
