Inflammation, obesity, and the promise of immunotherapy for metabolic disease.
Inflammation, obesity, and the promise of immunotherapy for metabolic disease.
复制标题
炎症、肥胖和代谢疾病免疫疗法的前景。
DOI：
10.1016/j.soard.2012.07.010
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
O'Rourke,RobertW
中科院分区：
文献类型：
--
作者：
O'Rourke,RobertW
Why do obese patients get sick? What underlies the pathogenesis of the many diseases associated with obesity? As recently as fifty years ago, the answer was mechanical stress on a variety of organ systems from increased body weight. But while this may explain osteoarthritis and venous stasis disease, it is not a satisfying explanation for diabetes, liver disease, allergic disease, cancer, and the many other diseases that are increased in incidence in obesity. What is it about excess adipose tissue that causes metabolic disease? The answer lies in one of the most important realizations in the field of obesity in the past twenty years: that obesity is associated with a state of chronic systemic inflammation and this inflammatory state, this hyper-activation of the immune system, underlies the pathogenesis of virtually every metabolic disease that afflicts the obese.One of the most exciting recent papers came from investigators at the University of Pennsylvania, who treated patients with end-stage leukemia with their own immune T-cells, genetically modified in the test tube to target leukemic cells. This high-tech immunotherapy achieved durable and complete remission in the majority of a small group of subjects who were otherwise expected to live only months, and has generated much excitement and hope (1). Manipulating physiologic processes as fundamental as the immune system also entails risk. In 2006, Tegenero Inc., a German Biotech company, administered a monoclonal antibody designed to treat autoimmune disease to human volunteers in a Phase I safety trial. Despite prior safety testing in rodents and primates, within minutes of administration all subjects experienced a “cytokine storm”, a hyper-activation of the immune system, went into multi-system organ failure, and required months of treatment in the intensive care unit (2). This incident generated much scrutiny and speaks to the perils of immunotherapy. While these anecdotes may seem unrelated to obesity and metabolic disease, I would suggest that the same ravages of the immune system that the Tegenero subjects experienced also afflict obese patients, but play out over years rather than hours or days. Furthermore, the same hope that immunotherapy provides for patients with cancer also exists for those with metabolic disease.
