CYTOKINES AS ENDOGENOUS MEDIATORS OF CANCER CACHEXIA

厌食症、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 仍然不为人所知。这个应用程序提出了厌食症， 患者的瘦组织和体脂与肝脏急性期反应 或患有癌症的实验动物可以部分归因于 不适当或过度产生细胞因子，包括白细胞介素1 α或β(IL-1)、肿瘤坏死因子-α(TNF-α/cachectin) 和/或白介素6(干扰素-β2)。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 小鼠器官中的附属细胞、血单核细胞或巨噬细胞 网状内皮系统可能自发释放一种或多种 这些细胞因子。因此，在这一应用中，细胞因子的产生(IL- 1.肿瘤坏死因子-α和白介素6)将直接在肿瘤中被检测 通过测量恶病质小鼠和体重减轻患者的数量 细胞因子特异性mRNA和免疫反应蛋白的存在，以及来自 荷瘤小鼠网状内皮系统的器官。在……里面 此外，为了确定是否生产一个或多个这些 细胞因子直接导致癌症恶病质的发展， 特异性中和多克隆和单抗 这些细胞因子和/或它们的组织受体将在体内给药 以确定是否可以阻断荷瘤小鼠的作用 这些细胞因子可以减轻或预防高血压的严重程度。 癌症恶病质的发展。因此，这一行动的具体目标是 应用于确定肿瘤特异性细胞因子或相关细胞因子 在实验和人类癌症中普遍发现的是，无论是 细胞因子来自肿瘤或宿主，最后，无论宿主 采食量、屠体蛋白质和脂肪组成以及肝脏的变化 急性时相反应可归因于不适当的生产 这些细胞因子。

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.