During the febrile response to intravenous endotoxin, there appears in the circulation an endogenous pyrogen, the properties of which are indistinguishable from those of the fever-producing substance contained in polymorphonuclear leucocytes (1, 2). Whereas most of the injected endotoxin is cleared from the blood stream during the latent period, the endogenous factor becomes demonstrable with the onset of fever and is present in a concentration which parallels the degree of pyrexia (2). The establishment of these facts has led to the concept that the hypothalamic stimulus which causes endotoxin fever is provided, not by the injected endotoxin itself, but rather by the endogenous pyrogen released from toxin-injured leucocytes (2, 3).Despite the numerous experimental observations which support it (3, 4), the endogenous pyrogen hypothesis has been challenged (5, 6) on the grounds that during endotoxin fever endogenous pyrogen was not demonstrable in the sera of animals previously made leucopenic with nitrogen mustard. The apparent absence of the circulating endogenous factor under these circumstances has been interpreted as evidence against the thesis that it plays a central role in endotoxin fever (5-13).Because of the importance which has been placed upon this evidence (5-13), it has been reexamined in the present study.
MethodsElimination of Extraneous Pyrogens.--All glassware and needles were rendered pyrogenfree by exposure to 180°C for 2 hours. Normal saline was autoclaved and was demonstrated to be non-pyrogenic.
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