PARASITE INDUCED CATABOLISM IN MAMMALS

哺乳动物的寄生虫和细菌入侵与 宿主常见代谢紊乱的数量。 其中一 是诱导分解代谢状态，当延长时， 导致恶病质、休克和死亡。 一种巨噬细胞产物， 恶病质，这是响应T. 布鲁塞。 柏氏青霉 和内毒素，抑制酶的合成 体内脂肪细胞和3 T3-L1前脂肪细胞的脂蛋白脂酶 体外最近被隔离了。 小鼠恶病质的微测序和随后的克隆揭示了 恶病质素与肿瘤坏死因子（TNF）相同。 在过去的几年里，一些生物活动 与恶病质有关的细菌。 这些都 包括选择性地关闭 特定的合成代谢基因，促进厌食，体重减轻和贫血， 诱发发热、出血性坏死、肾小管坏死和致死 冲击. 抗恶病质/TNF抗体可预防 小鼠会感染内毒素，狒狒会感染致命的败血症。 因此它 似乎宿主对入侵反应过度， cachectin/TNF。 此外，最近还发现了一种新的单核细胞因子， 并被克隆出来，命名为巨噬细胞炎性蛋白 （MIP）。 这种蛋白质可以在体外引起中性粒细胞迁移， in vivo. 在下一个资助期，对恶病质/TNF产生的研究， 体外和体内作用机制，特别分析 它在促进恶病质和休克方面的作用将继续下去。 这些 研究将包括详细分析控制点， 脂蛋白脂酶和葡萄糖的转录和翻译 在3 T3-L1细胞中的转运蛋白。 可能的相互作用 恶病质/TNF与其他细胞因子（IL 1和干扰素γ） 将评估在体内诱导恶病质。 动物模型 还将检查恶病质中恶病质素/TNF的可能作用 通过施用抗恶病质抗体。 进一步的工作还 与MIP计划，以确定其他生物功能及其 与其他单核细胞的关系 此外，搜索将 对于巨噬细胞产生的其他单核因子， 入侵。 这些研究应该提供新的见解， 与慢性感染相关的恶病质的治疗。

Parasitic and bacterial invasion of mammals is associated with a number of common metabolic derangements of the host. One of these is the induction of a catabolic state, which when prolonged, can lead to cachexia, shock and death. A macrophage product, cachextia, which is made in response to T. brucei. P. berghei. and endotoxin, that inhibits the synthesis of the enzyme lipoprotein lipase of adipocytes in vivo and 3T3-Ll pre-adipocytes in vitro. has been recently isolated. Microsequencing and subsequent cloning of mouse cachectin revealed that cachectin was identical to tumor necrosis factor (TNF). During the past few years, a number of biological activities associated with cachectin have been identified. These have included the ability to selectively turn off transcription of specific anabolic genes, promote anorexia, weight loss and anemia, induce fever, hemorrhagic necrosis, tubular necrosis and lethal shock. Antibodies to cachectin/TNF can prevent the lethality of mice to endotoxin and baboons to lethal septicemia. It thus appears that host overreacts to invasion and produces toxic amounts of cachectin/TNF. In addition, a new monokine has been recently identified, isolated and cloned which has been named macrophage inflammatory protein (MIP). This protein can elicit neutrophil migration in vitro and in vivo. In the next grant period, studies of cachectin/TNF production, mechanism of action in vitro and in vivo with special analysis on its role in promoting cachexia and shock, will be continued. These studies will include detailed analysis of control points for transcription and translation of lipoprotein lipase and the glucose transporter in 3T3-Ll cells. The possible interaction of cachectin/TNF with other cytokines (IL1 and Interferon gamma) of inducing cachexia in vivo will be assessed. Animal models of cachexia will also be examined for possible role of cachectin/TNF by administering anti-cachectin antibodies. Further work is also planned with MIP to determine other biological functions and its relationship to other monokines. In addition, a search will continue, for other monokines produced by macrophages in response to invasion. These studies should give new insight into therapeutics of the cachexia associated with chronic infections.