Comparison of endogenous pyrogens from human and rabbit leucocytes utilizing Sephadex filtration.

A fever-producing substance derived from rabbit exudate leucocytes was first described in 1953 by Bennett and Beeson.' The subsequent demonstration of pyrogens with similar biologic properties derived from other variously stimulated leucocytes' or present in the blood of febrile rabbits7 has led to the concept of a single pyrogenic substance, termed endogenous pyrogen. Most investigations of the nature of this material have been carried out with leucocyte pyrogen released from rabbit exudate polymorphonuclear leucocytes incubated in saline, and assayed for pyrogenic activity by injection into rabbits. These studies!' have demonstrated that endogenous pyrogen is moderately heat-stable, precipitated by perchloric acid, not extractable in butanol, and destroyed by treatment with trypsin or pepsin. It is believed to be a small protein, with a molecular weight of 10,000 to 20,000, and with perhaps a lipid moiety."' Recently a number of different types of cells have been found to release pyrogenic material following appropriate stimulation. From rabbits, such cells include blood leucocytes,"' lung macrophages,5 exudate monocytes,t cells from lymph node, spleen,' and liver Kupffer cells;1" and from man, circulating polymorphonuclear leucocytess and monocytes.'" Initial studies on the pyrogenic material released from human blood leucocytes after phagocytosis indicated that pyrogenic activity was destroyed by incubation with trypsin.'5 Pyrogen derived from human cells produces fever in rabbits,"n and recently biologic cross-reactivity has also been reported for pyrogens from several animal species.'7 It seemed of interest, therefore, to compare the molecular weight of pyrogens from human and rabbit cells, as well as from polymorphonuclear leucocytes and mononuclear cell types, by the technique of sephadex filtration.