Leucocytic Pyrogen generated by Endotoxin

Abstract

LEUCOCYTIC pyrogen is a low molecular weight protein synthesized by polymorphonuclear and mononuclear leucocytes in response to certain stimuli. The fever accompanying many bacterial and viral infections is thought to be caused by the release of this material from host leucocytes and its action at the thermoregulatory centre of the brain¹. Pyrogen is not preformed in leucocytes. In in vitro experiments, it appears in the extracellular fluid only on incubating intact leucocytes at 37° C, when a potent stimulus is endotoxin or bacterial lipopolysaccharide². The well known pyrogenicity of endotoxin is best explained by its action on circulating leucocytes, but the mechanism is not known. It is usually assumed that endotoxin liberates a bound form of pyrogen or converts a propyrogen to an active form without itself entering into pyrogen formation. We shall describe a leucocytic-type pyrogen generated by incubating endotoxin with inactive leucocytic pyrogen preparations, which suggests that endotoxin contributes a building block for the synthesis of leucocytic pyrogen.