CRH MEDIATED ANOREXIA CACHEXIA

艾滋病是一种以严重免疫缺陷为特征的多方面疾病。 和身体消瘦(恶病质)。厌食症，包括绝对的 食物摄入量减少或摄入量相对于能量不足 支出，被广泛认为是艾滋病的主要危险因素 浪费。我们将检验促肾上腺皮质激素释放激素的假设 促肾上腺皮质激素释放激素(CRH)是一种有效的摄食抑制物，是一种重要的调节因子。 厌食症和荷尔蒙变化会导致消瘦综合症。CRH 可能通过几种不同的机制在艾滋病中升高，包括 艾滋病毒或继发感染刺激的细胞因子表达增加，以及 由于原发性肾上腺功能不全，糖皮质激素抑制消失。 我们推测蛋白质营养不良也会导致慢性肾功能衰竭。 监管失调。血浆皮质醇升高，在一些艾滋病中有记录 患者，也提示CRH驱动力增加，并可能本身 助长浪费。我们将控制啮齿动物的肾上腺激素水平 耗竭模型(营养剥夺或脑室内IL- 1β输液)，以评估营养不良的潜在作用-或 细胞因子诱导的艾滋病恶病质CRH的产生。我们将测试 营养补充剂或食欲刺激剂 至少部分通过改变CRH来改善恶病质。我们将进一步 通过比较下丘脑-CRH对这些效应的依赖程度 CRH正常和CRH缺陷者的垂体-肾上腺(HPA)和摄食活动 (-/-，基因敲除)小鼠在营养限制或脑室注射IL-1期间。 这项工作将阐明可能涉及消耗的内分泌信号 在艾滋病和营养方面取得成功的条件 减轻恶病质。

AIDS is a multifaceted disease characterized by severe immunodeficiency and body wasting (cachexia). Anorexia, comprising either absolute decreases in food intake or inadequate intake relative to energy expenditure, is widely recognized to be a major risk factor in AIDS wasting. We will test the hypothesis that corticotropin-releasing hormone (CRH), a potent inhibitor of feeding, is a significant mediator of the anorexia and hormonal changes contributing to wasting syndromes. CRH could be elevated by several different mechanisms in AIDS, including elevated cytokine expression stimulated by HIV or secondary infection, and loss of glucocorticoid inhibition due to primary adrenal insufficiency. We postulate that protein malnutrition can also result in CRH dysregulation. Elevated plasma cortisol, documented in some AIDS patients, is also suggestive of increased CRH drive and may itself contribute to wasting. We will control adrenal hormone levels in rodent models of wasting (nutrient deprivation or intracerebroventricular IL- 1beta infusion) to evaluate the potential role of malnutrition- or cytokine-induced CRH production in AIDS-related cachexia. We will test the possibility that nutritional supplementation or appetite stimulants ameliorate cachexia at least in part via changes in CRH. We will further assess the CRH dependence of these effects by comparing hypothalamic- pituitary-adrenal (HPA) and feeding activity in normal and CRH-deficient (-/-, knock-out) mice during nutrient restriction or icv IL-1 infusion. This work will elucidate endocrine signals potentially involved in wasting in AIDS and the conditions under which alimentation may be successful in attenuating cachexia.