Possible involvement of lymphocyte activating factor(LAF) as an endogenous pyrogen in fever induced by the cell wall skeleton of Nocardia rubra(N-CWS).

Abstract

We investigated whether interleukin-1 (IL-1) acts as an endogenous pyrogen (EP) on the fever caused by the cell wall skeleton of Nocardia rubra (N-CWS) in guinea pigs. IL-1 activity was expressed as potency of lymphocyte activating factor (LAF). When guinea pig peritoneal macrophages were pulse-stimulated with N-CWS (1-100 micrograms/ml), dose-dependent LAF activity was detected in the supernatants after culture for 4 h. Gel filtration of the culture supernatants on Sephadex G-200 showed that the fractions with LAF activity were not the same as those with cytotoxic activity for L-929 cells, which was measured as an index of tumor necrosis factor (TNF) in parallel with LAF activity. Pyretic activity was detected both in the fractions with LAF activity and in those with cytotoxic activity for L-929 cells. Furthermore, when these macrophages were pulse-stimulated again, this time with the supernatant obtained from macrophages previously pulse-stimulated with N-CWS, LAF and cytotoxic activity for L-929 cells continued to be released from the macrophages. We suggest that IL-1 might be a possible EP in the process of fever elicited by N-CWS, and that such an EP stimulates the macrophages to release further IL-1 or TNF. The resultant long-lasting fever would thus be caused by the continuous release of an EP.