The Common Mediator of Shock, Cachexia, and Tumor Necrosis

Complement-mediated injury, anaphylactic shock, and cell-mediated hypersensitivity reactions are often cited as disease processes in which the immune system has worked to the detriment of the host. Cachectin, acting alone and in concert with other mediators, is capable of evoking a “shock” state, in which hypotension, derangements of lipid and glucose metabolism, metabolic acidosis, and end-organ damage may injure or kill the host. When administered at low doses over a prolonged period, cachectin induces a state of anorexia and wasting similar to cachexia as it occurs in chronic infection or cancer. In part through its effects on vascular endothelial cells, cachectin can induce a coagulopathic state localized to certain vascular beds, leading to hemorrhagic necrosis of various tissues. This effect is particularly pronounced in certain tumor vessels, such that the hormone was originally recognized by its ability to provoke the hemorrhagic infarction of transplantable neoplasms, and was termed “tumor nec rosis factor.” On the one hand, as “cachectin,” the molecule was purified as a mediator of shock and wasting in chronic disease. On the other hand, as “tumor necrosis factor,” the molecule was isolated as a mediator of one of the “beneficial” effects of bacterial endotoxin, known as “induction of tumor necrosis.”