Hersoug L-G, Linneberg A
Research Centre for Prevention and Health, Copenhagen County, Denmark.
Allergy. 2007 Oct;62(10):1205-13. doi: 10.1111/j.1398-9995.2007.01506.x.
There is increasing epidemiological evidence that obesity increases the risk of asthma, atopic, and autoimmune diseases. We hypothesize that the increase in these diseases is caused, at least in part, by decreased immunological tolerance as a consequence of immunological changes induced by adipokines (e.g. leptin and adiponectin) and cytokines [e.g. interleukin 6 (IL6) and tumor necrosis factor alpha (TNFalpha)] secreted by white adipose tissue. The increasing body weight increases the levels of circulating IL6, leptin, and TNFalpha. IL6 and leptin down-regulate the activity of regulatory T-lymphocytes (Tregs). Additionally, adiponectin, which decreases with increasing obesity, down-regulates the secretion of IL10 from macrophages and adipocytes. These changes in IL6, leptin, and IL10 decrease the regulatory effect of Tregs resulting in decreased immunological tolerance to antigens. In pregnant women, these obesity-induced immunological changes might be transmitted to the fetus by epigenetic inheritance thereby increasing the risk of atopic disease. We propose that obesity results in immunological changes resulting in decreased immunological tolerance to antigens and skewing of the immune system towards a Th2 cytokine profile increasing the risk of allergy and other immune-mediated diseases. Furthermore, this hypothesis offers a unifying explanation for the observation that older siblings appear to confer protection against atopic diseases, preeclampsia, and certain autoimmune diseases. More studies are definitely needed to explore further the immunological effects of obesity and its possible effects on allergic disease.
越来越多的流行病学证据表明，肥胖会增加患哮喘、特应性疾病和自身免疫性疾病的风险。我们推测，这些疾病的增加至少部分是由于白色脂肪组织分泌的脂肪因子（如瘦素和脂联素）和细胞因子[如白细胞介素6（IL6）和肿瘤坏死因子α（TNFα）]诱导的免疫变化导致免疫耐受性降低所致。体重增加会使循环中的IL6、瘦素和TNFα水平升高。IL6和瘦素会下调调节性T淋巴细胞（Tregs）的活性。此外，随着肥胖程度增加而减少的脂联素会下调巨噬细胞和脂肪细胞中IL10的分泌。IL6、瘦素和IL10的这些变化会降低Tregs的调节作用，导致对抗原的免疫耐受性降低。在孕妇中，这些由肥胖引起的免疫变化可能通过表观遗传传递给胎儿，从而增加患特应性疾病的风险。我们认为，肥胖会导致免疫变化，从而降低对抗原的免疫耐受性，并使免疫系统偏向Th2细胞因子谱，增加过敏和其他免疫介导疾病的风险。此外，这一假说为年长的兄弟姐妹似乎能提供针对特应性疾病、先兆子痫和某些自身免疫性疾病的保护这一观察结果提供了一个统一的解释。显然需要更多的研究来进一步探索肥胖的免疫效应及其对过敏性疾病可能产生的影响。
