Lord G M, Matarese G, Howard J K, Baker R J, Bloom S R, Lechler R I
Imperial College School of Medicine, Department of Immunology, The Hammersmith Hospital, London, UK.
Nature. 1998 Aug 27;394(6696):897-901. doi: 10.1038/29795.
Nutritional deprivation suppresses immune function. The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight. Circulating levels of this adipocyte-derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators. The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob) or its receptor (db/db), has never been explained. Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases. We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells. Leptin increased Th1 and suppressed Th2 cytokine production. Administration of leptin to mice reversed the immunosuppressive effects of acute starvation. Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.
营养缺乏会抑制免疫功能。肥胖基因的克隆及其蛋白产物瘦素的鉴定，为深入了解下丘脑对体重的调节提供了基础。这种源自脂肪细胞的激素的循环水平与脂肪量成正比，但可能会因禁食而迅速降低，或因炎症介质而升高。目前已知瘦素（ob/ob）或其受体（db/db）有缺陷的小鼠的T细胞免疫受损，但其原因从未得到解释。细胞介导的免疫受损和瘦素水平降低都是人类体重过低的特征。事实上，营养不良易导致因传染病死亡。我们在此报告，瘦素对T淋巴细胞反应有特定作用，能差异性地调节初始T细胞和记忆T细胞的增殖。瘦素增加了Th1细胞因子的产生并抑制了Th2细胞因子的产生。给小鼠注射瘦素可逆转急性饥饿的免疫抑制作用。我们的研究结果表明瘦素在将营养状况与相关细胞免疫功能联系起来方面有新作用，并提供了一种分子机制来解释饥饿时观察到的免疫功能障碍。
