TY - JOUR
T1 - Tumor necrosis, cachexia, shock, and inflammation
T2 - A common mediator
AU - Beutler, B.
AU - Cerami, A.
PY - 1988
Y1 - 1988
N2 - A variety of disease states appear to result from the overexpression of immune mechanisms that orginally evolved for the protection of the host. During the past few years, it has become clear that ceveral host proteins can, of themselves, 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 parenchymal 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 cachectin/tumor necrosis factor serves as a general mediator of inflammatory processes, 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.
AB - A variety of disease states appear to result from the overexpression of immune mechanisms that orginally evolved for the protection of the host. During the past few years, it has become clear that ceveral host proteins can, of themselves, 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 parenchymal 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 cachectin/tumor necrosis factor serves as a general mediator of inflammatory processes, 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.
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U2 - 10.1146/annurev.bi.57.070188.002445
DO - 10.1146/annurev.bi.57.070188.002445
M3 - Review article
C2 - 3052281
AN - SCOPUS:0023944339
SN - 0066-4154
VL - 57
SP - 505
EP - 518
JO - Annual review of biochemistry
JF - Annual review of biochemistry
ER -