Relation between complement and the febrile response of guinea pigs to systemic endotoxin

We reported recently that the complement (C) system may play a role in the febrile response of guinea pigs to intravenous lipopolysaccharide (LPS) adm inistration because C depletion abolished the LPS-induced rise in core temp erature (T-c). The present study was designed to investigate further the re lation between C reduction [induced by cobra venom factor (CVF); 20, 50, 10 0, and 200 U/animal iv] and the fever of adult, conscious guinea pigs produ ced by LPS injected intravenously (2 mu g/kg) or intraperitoneally (8, 16, 32 mu g/kg) 18 h after CVF; control animals received pyrogen-free saline. S erum C levels were measured as total hemolytic C activity before and 18 h a fter CVF injection and expressed as CH100 units. In other experiments, seru m C levels were determined at various intervals after the intravenous and i ntraperitoneal injections at different doses of LPS alone. LPS produced fev ers generally of similar heights but of different onset latencies and durat ions, depending on the dose and route of administration. CVF caused dose-re lated reductions in serum C, from similar to 1,136 U to below detection. Th ese reductions proportionately attenuated the fevers induced by intraperito neal LPS, but not by intravenous LPS. Intravenous and intraperitoneal LPS p er se caused reductions in serum C of 25 and 40%, respectively, indicating activation of the C cascade. These decreases were transient, however, occur ring early during the febrile rise similar to 30 min after LPS injection. T hese data thus support the notion that the C system may be critically invol ved in the febrile response of guinea pigs to systemic, particularly intrap eritoneal, LPS.