Further comparisons of endogenous pyrogens and leukocytic endogenous mediators

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Abstract
Rabbit macrophages produce 2 biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a MW of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16 h rabbit peritoneal exudates. These acute peritoneal exudates were produced by i.p. injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37.degree. C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma Fe and Zn levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with pI between 4.5-5.0. These proteins are produced by macrophages in the lung, liver or in chronic peritoneal exudates. In these experiments, the lower-pI endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens had leukocytic endogenous mediator activity in mice, but were completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma Fe and increased blood neutrophils, but failed to elevate plasma fibrinogen.