506 BEUTLER & CERAMI selves, cause injury by triggering the release of terminal inflammatory mediators, and altering host metabolism. Prominent among these cytokines is a macrophage-derived protein known as cachectin. Cachectin, acting alone and in concert with other mediators, is capable of evoking a" shock" state, in which hypotension, derangements of host lipid and glucose metabolism, metabolic acidosis, and widespread neutrophil activation lead to the demise of the organism. Cachectin also can induce a state of anorexia and wasting strongly reminiscent of cachexia as it occurs in chronic infectious and neoplastic disease. Moreover, perhaps through induction of a localized coagulopathic state, cachectin causes hemorrhagic necrosis of certain paren chymal organs, and of certain tumors. This latter effect led to use of the term" tumor necrosis factor" to denote this cytokine. It would appear that cachec tin/tumor necrosis factor serves as a general mediator of inflammatory pro cesses, and that cachectin, as well as a limited number of other cytokines, may be essential elements in the pathogenesis of many human and animal diseases.