Tracey K J, Lowry S F, Cerami A
Laboratory of Medical Biochemistry, Rockefeller University, New York, NY 10021.
Ciba Found Symp. 1987;131:88-108. doi: 10.1002/9780470513521.ch7.
Mammals infected with parasitic, bacterial or viral organisms or bearing tumours characteristically display a catabolic state and weight loss which can advance to cachexia (or wasting), shock and death. Although the phenomenon is commonly observed in many parasitic diseases its mechanism is not understood. We have identified and isolated a macrophage protein, cachectin, as the molecule that may be responsible for cachexia and shock. Cachectin is produced by macrophages in response to endotoxin or a number of other bacterial or protozoal products. The released cachectin acts as a hormone, binding to specific high affinity receptors and eliciting biological responses. In the adipocyte anabolic enzymes such as lipoprotein lipase are suppressed through the selective inhibition of mRNA production. An intriguing aspect of cachectin is its pivotal role in the pathogenesis of endotoxin-induced shock. Cachectin causes fever and anorexia and can induce lethal shock and tissue injury in experimental animals. During its chemical characterization cachectin was shown to be identical to tumour necrosis factor (TNF), a macrophage protein that kills tumour cells. This finding emphasizes the extensive range of effects associated with this protein. Cachectin has many properties in common with interleukin 1 but binds to a different receptor and lacks structural homology. Presumably, low levels of cachectin help the host in its battle to remove invasive pathogens, but extensive production of cachectin can lead to shock and catabolic stress hormone responses. These findings have added a new dimension to the biological properties of cachectin, its production, and its role in cachexia and shock.
感染寄生虫、细菌或病毒病原体或患有肿瘤的哺乳动物通常会呈现分解代谢状态并体重减轻，进而可能发展为恶病质（或消瘦）、休克甚至死亡。尽管这种现象在许多寄生虫病中普遍存在，但其机制尚不清楚。我们已经鉴定并分离出一种巨噬细胞蛋白——恶病质素，它可能是导致恶病质和休克的分子。恶病质素由巨噬细胞对内毒素或许多其他细菌或原生动物产物作出反应而产生。释放出的恶病质素作为一种激素，与特定的高亲和力受体结合并引发生物学反应。在脂肪细胞中，诸如脂蛋白脂肪酶等合成代谢酶会通过对mRNA产生的选择性抑制而受到抑制。恶病质素一个有趣的方面是它在内毒素诱导的休克发病机制中起关键作用。恶病质素会引起发热和厌食，并能在实验动物中诱发致命性休克和组织损伤。在对其进行化学特性分析的过程中，恶病质素被证明与肿瘤坏死因子（TNF）相同，TNF是一种能杀死肿瘤细胞的巨噬细胞蛋白。这一发现强调了与该蛋白相关的广泛效应。恶病质素与白细胞介素1有许多共同特性，但它与不同的受体结合且缺乏结构同源性。据推测，低水平的恶病质素有助于宿主对抗入侵的病原体，但恶病质素的大量产生会导致休克和分解代谢应激激素反应。这些发现为恶病质素的生物学特性、其产生及其在恶病质和休克中的作用增添了新的维度。
