The pathophysiology of tumor necrosis factors

P Vassalli - Annual review of immunology, 1992 - annualreviews.org
P Vassalli
Annual review of immunology, 1992annualreviews.org
Tumor necrosis factor (TNF) came to birth in a strange way. It made its entry into the world of
biology and medicine when Lloyd Old discovered that the capacity to induce, in vivo and in
vitro, the necrosis of some mouse tumors could be ascribed to a factor (rapidly identified as a
protein) present in the blood after LPS injection (1). Then, at what may appear as an
unsurmountable biological distance but what geographically was a very close event
(occurring in New York City virtually on the other side of the street), Anthony Cerami …
Tumor necrosis factor (TNF) came to birth in a strange way. It made its entry into the world of biology and medicine when Lloyd Old discovered that the capacity to induce, in vivo and in vitro, the necrosis of some mouse tumors could be ascribed to a factor (rapidly identified as a protein) present in the blood after LPS injection (1). Then, at what may appear as an unsurmountable biological distance but what geographically was a very close event (occurring in New York City virtually on the other side of the street), Anthony Cerami discovered that the intriguing state of cachexia associated with hypertriglyceridemia presented by rabbits chronically infected with Trypanosomia brucei results from the presence of a serum protein which he called" cachectin." Purification of cachectin by A. Cerami and B. Beutler led them to realize that it is also an essential mediator in the state of shock induced by LPS injection in mice and is the same molecule as TNF (2, 3). It required little time for these three parents to recognize that their common child, with its so disparate talents, was unusually gifted. What they could not foresee was that, within a very few years, TNF would turn out to be a child prodigy, eliciting, because of its diverse effects, the publication of several papers per day. Somewhat ironically, it appears now that TNF rarely induces in vivo direct cytolysis of natural tumors (it can even be made by them), that it may not play a significant role in the cachexia most commonly observed in humans, that resulting from cancer, and that the critical role ofTNF in shock is shared by other mediators, particularly interleukin 1 (IL-l), its frequent com-
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