CYTOKINES AS ENDOGENOUS MEDIATORS OF CANCER CACHEXIA

细胞因子作为癌症恶病质的内源性介质

• 批准号: 3196890
• 负责人: LYLE L MOLDAWER
• 金额: $ 8.14万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3196890
• 关键词: antibody receptor; body weight; cachexia; cytokine; immunocytochemistry; interleukin 1; interleukin 6; laboratory mouse; monoclonal antibody; nutrient intake activity; nutrition aspect of cancer; nutrition related tag; tumor necrosis factor alpha; weight loss

Anorexia, weight loss and cachexia are the most visibly recognizable symptoms associated with cancer. However, the causes of cancer cachexia remain unknown. This application proposes that the anorexia, losses of lean tissue and body fat, and the hepatic acute phase response in patients or experimental animals with cancer can be attributed in part to an inappropriate or excessive production of cytokines, including interleukin-1 alpha or beta (IL-1), tumor necrosis factor-alpha (TNF-alpha/cachectin) and/or interleukin-6 (interferon-beta2). Experimental evidence suggests that either the tumor itself or tumor-infiltrating macrophages and other accessory cells, blood monocytes, or macrophages contained in organs of the reticuloendothelial system may be spontaneously releasing one or more of these cytokines. Therefore, in this application, cytokine production (IL- 1. TNF-alpha and IL-6) will be evaluated directly in the tumors of cachectic mice and of weight-losing patients by measuring both the quantity of cytokine-specific mRNA and immune reactive protein present, and from organs of the reticuloendothelial system of tumor-bearing mice. In addition, to determine whether the production of one or more of these cytokines is contributing directly to the development of cancer cachexia, specific neutralizing polyclonal and monoclonal antibodies directed against these cytokines and/or their tissue receptors will be administered in vivo to tumor-bearing mice in order to determine whether blocking the actions of these cytokines can either reduce the severity of or prevent the development of cancer cachexia. Thus, the specific goal of this application is to determine whether tumor specific or associated cytokine production are common findings in experimental and human cancer, whether the cytokines are of tumor or host origin, and finally, whether the host changes in food intake, carcass protein and fat composition, and hepatic acute phase response can be attributed to the inappropriate production of these cytokines.

厌食、体重减轻和恶病质是最明显的 与癌症相关的症状。 然而，癌症恶病质的原因 仍然未知。 本申请提出，厌食症，损失的 瘦组织和体脂，以及患者的肝脏急性期反应 或实验动物患癌症的部分原因是 细胞因子（包括白细胞介素-1）产生不当或过量 α或β（IL-1）、肿瘤坏死因子-α（TNF-α/恶病质） 和/或白细胞介素-6（干扰素-β 2）。 实验证据表明 无论是肿瘤本身还是肿瘤浸润性巨噬细胞和其他 辅助细胞、血液单核细胞或巨噬细胞包含在器官中， 网状内皮系统可以自发地释放一种或多种 这些细胞因子。 因此，在本申请中，细胞因子产生（IL-10）是一个非常重要的因素。 1. TNF-α和IL-6）将直接在以下肿瘤中进行评估： 通过测量恶病质小鼠和减肥患者的 存在的精氨酸特异性mRNA和免疫反应蛋白， 荷瘤小鼠网状内皮系统的器官。 在 此外，为了确定其中一个或多个的生产是否 细胞因子直接促进癌症恶病质的发展， 特异性中和多克隆和单克隆抗体， 这些细胞因子和/或它们的组织受体将在体内施用 以确定是否阻断了 这些细胞因子可以减轻或预防 癌症恶病质的发展。 因此，这一具体目标 本发明的应用是确定肿瘤特异性或相关的细胞因子 在实验和人类癌症中， 细胞因子是肿瘤或宿主来源的，最后，宿主是否 摄食量、胴体蛋白质和脂肪组成以及肝脏的变化 急性期反应可归因于不适当的生产， 这些细胞因子。