Complement does not mediate the febrile responses of guinea pigs to muramyl dipeptide and polyriboinosinic–polyribocytidylic acid

Abstract

The complement (C) system and Kupffer cells (Kc) play critical roles in the febrile response of guinea pigs to i.p.-, but not i.v.-injected lipopolysaccharide (LPS). We have investigated whether C and Kc may also mediate this species’ febrile response to muramyl dipeptide (MDP) and polyriboinosinic–polyribocytidylic acid (poly I:C), two other exogenous pyrogens. Both i.v. and i.p. injections of MDP (150 μg/kg) caused initial, transient falls (0.6°C after 90 min by both routes), then rises (0.8°C at 220 and 0.5°C at 200 min, respectively) in core temperature ( T c). Cobra venom factor (CVF)-induced reductions in C variably affected these courses, but the fever indices and the reductions in serum C activity were not correlated. In addition, neither the i.v. nor the i.p. injection of MDP per se induced a significant change in the serum C activity. The i.v. injection of poly I:C (30 μg/kg) caused a 0.6°C T c rise which started within 30 min, peaked at 60 min, and recovered in 5 h. The i.p. injection of poly I:C (50 μg/kg) caused a fever similar to that produced by the i.v. injection, but with a later onset, starting at 90 min after drug administration. Again, C reduction did not affect the overall fever indices, although some individual responses were slightly attenuated. The i.v. injection of poly I:C per se also did not affect the serum C activity. These results indicate that, in contrast to its role in i.p. LPS-induced fever, C is not involved in the febrile responses of guinea pigs to both i.v. and i.p. MDP or poly I:C.