Leptin in fibroproliferative acute respiratory distress syndrome: not just a satiety factor.
Leptin in fibroproliferative acute respiratory distress syndrome: not just a satiety factor.
复制标题
纤维增生性急性呼吸窘迫综合征中的瘦素：不仅仅是饱足感因素。
DOI：
10.1164/rccm.201102-0286ed
复制
发表时间：
2011
影响因子：
24.7
通讯作者：
Standiford,TheodoreJ
中科院分区：
文献类型：
--
作者：
Moss,Marc;Standiford,TheodoreJ
The acute respiratory distress syndrome (ARDS) is a devastating form of acute lung injury that occurs in critically ill patients. Early epidemiological studies identified several at-risk diagnoses that were associated with an increased susceptibility for the development of ARDS, including sepsis, major trauma, massive transfusion, and the aspiration of gastric contents (1, 2). However, only 20 to 40% of patients with these at-risk diagnoses eventually develop ARDS. Therefore, other factors including pre-existing co-morbid conditions may influence the vulnerability of a critically ill patient to develop ARDS. Diabetes mellitus is one pre-existing disorder that has biologically plausible reasons to alter the pathogenesis of ARDS. Three different clinical studies have reported an association between a history of diabetes and a decreased risk of developing ARDS with very consistent odds ratios ranging from 0.33 to 0.58, even after adjustment for several important confounding variables, including age, sex, and severity of illness (3–5). Combining the 961 patients enrolled into these observational studies, the incidence of ARDS was 26.3%(66/251) in patients with diabetes and 38.3%(272/710) in those patients without diabetes (P, 0.0005; odds ratio, 0.57; 95% confidence interval, 0.41–0.79). Though hyperglycemia is a common occurrence in diabetic patients, these studies did not provide conclusive evidence that the mechanism by which diabetes diminishes the risk of developing ARDS is related to the effects of hyperglycemia alone. The protective effects of diabetes on the development of acute lung injury have also been reproduced in various animal models. After exposure to intratracheal endotoxin, type I diabetic rats demonstrated less lung injury, reduced concentrations of tumor necrosis factor, interleukin-1, and decreased neutrophils in the bronchoalveolar lavage fluid (6, 7). Similarly, type II diabetic rats exhibited less protein leakage in the lung after intratracheal exposure to lipopolysaccharide (LPS)(8).It is likely that there are multiple mechanisms by which diabetes attenuates the susceptibility to develop ARDS. For example, type II diabetes is associated with a variety of immunomodulatory conditions, including insulin resistance, obesity, hyperleptinemia, and dyslipidemia. In addition, patients with diabetes receive specific medications that alter the systemic inflammatory response including insulin, peroxisome proliferator–activated receptor-g (PPAR-g), agonists, and metformin. Recently, leptin has emerged as a potentially important mediator of the pathogenesis of multiple lung diseases. Leptin is a protein that is synthesized and secreted primarily by white adipose cells and acts on the brain to decrease hunger. Leptin is also an important mediator of the inflammatory response (9). Disorders associated with reduced leptin production, such as malnutrition, are associated with an increased susceptibility to infection. Conversely, increased secretion of leptin is associated with the production of proinflammatory pathogenic cytokines. For example, increasing evidence suggests that the proinflammatory effects of leptin may contribute to the higher incidence of asthma in the obese population (10). Leptin resistance is present in more
