Purification and characterization of an endogenous pyrogen.

Many microbes and their products are capable of producing fever when injected intravenously in various laboratory animals. Recent studies, involving passive transfer of serum from febrile donor animals to normal recipients, have shown that most, if not all, these agents cause fever indirectly via liberation of a circulating pyrogen of endogenous origin.' To date, the source of endogenous pyrogen (EP) has been identified with certainty only in fevers induced by the endotoxins of Gram-negative bacteria. Several lines of evidence indicate that endotoxins liberate pyrogen from polymorphonuclear leukocytes.2'5 Granulocytic pyrogen has been partially purified and characterized by Wood and his colleagues.6 Viruses of the myxovirus group-mumps, influenza, and Newcastle disease virus-are among the most potent fever-inducing microbial agents known. When given intravenously, these viruses evoke large amounts of circulating pyrogen which is clearly distinct from virus and which appears to be the direct cause of this form of fever.7 The following studies were undertaken in an attempt to purify and characterize the endogenous pyrogen appearing in the serum of rabbits given NDV and to compare this pyrogen with leukocytic pyrogen obtained from acute inflammatory exudates.8"9 A method is described for the assay and purification of NDV-induced serum endogenous pyrogen (hereinafter referred to as NDV-EP) and various features of the febrile response have been correlated with dosage of the pyrogen. The biochemical properties of a partially purified preparation of NDV-EP are compared with those reported by Rafter, Collins, and Wood for granulocytic pyrogen.'