Cutolo Maurizio, Otsa Kati, Aakre Oivi, Sulli Alberto
Research Laboratory and Division of Rheumatology, Department of Immunology and Endocrinology, University of Genoa, Viale Benedetto XV, 16132 Genoa-I, Italy.
Ann N Y Acad Sci. 2005 Jun;1051:372-81. doi: 10.1196/annals.1361.079.
It is well known that some clinical signs and symptoms of rheumatoid arthritis (RA) vary within a day and between days; the morning stiffness that is observed in patients who have RA has become one of the diagnostic criteria of the disease. The circadian changes in the metabolism or nocturnal secretion of endogenous corticosteroids is certainly responsible, in part, for the time-dependent changes that are observed in the inflammatory response and related clinical symptoms. More recently, melatonin (mLT), another circadian nocturnal hormone that is the secretory product of the pineal gland, has been implicated in time-dependent inflammatory reactions, with effects that are opposite of those of corticosteroids. Therefore, altered functioning of the hypothalamic-pituitary-adrenocortical axis (reduced corticosteroid production) and of the pineal gland (increased mLT production) found in RA patients seem to be important factors in the perpetuation and clinical circadian symptoms of the disease. Consistently, human proinflammatory Th1-type cytokine production (related to mLT stimulation) exhibits a diurnal rhythmicity, with peak levels during the night and early morning, at a time when plasma cortisol (inducing Th2-type cytokine production) is lowest and mLT is highest. Reduced daily light exposure as observed in northern Europe (Estonia), at least during the winter, might explain the higher and more prolonged mLT concentrations as well as some epidemiological features that are observed in northern European patients with RA versus southern European patients.
众所周知，类风湿关节炎（RA）的一些临床体征和症状在一天内以及不同日子之间会有所变化；RA患者出现的晨僵已成为该疾病的诊断标准之一。内源性皮质类固醇的代谢或夜间分泌的昼夜节律变化肯定在一定程度上导致了在炎症反应及相关临床症状中观察到的时间依赖性变化。最近，褪黑素（mLT），另一种由松果体分泌的昼夜节律性夜间激素，也被认为与时间依赖性炎症反应有关，其作用与皮质类固醇相反。因此，RA患者下丘脑 - 垂体 - 肾上腺皮质轴功能改变（皮质类固醇分泌减少）和松果体功能改变（mLT分泌增加）似乎是该疾病持续存在及出现临床昼夜症状的重要因素。一致的是，人类促炎Th1型细胞因子的产生（与mLT刺激有关）呈现昼夜节律性，在夜间和清晨达到峰值，此时血浆皮质醇（诱导Th2型细胞因子产生）最低而mLT最高。在北欧（爱沙尼亚）观察到的每日光照减少，至少在冬季，可能解释了北欧RA患者与南欧患者相比，mLT浓度更高且持续时间更长以及一些流行病学特征。
