Polyclonal antibodies to rat interleukin-6 attenuate fever in rats after burn injuries: a preliminary report

Rats with 50% total body surface area full-thickness burn injuries have sustained increases in body temperature without evidence of sepsis. In this animal model, the only known endogenous pyrogen consistently present in plasma is interleukin-6 (IL-6). We investigated the hypothesis that IL-6 acts as an endogenous pyrogen and produces the observed increase in body temperature. Body temperature and activity index were recorded every 5 minutes for control rats and rats with burns (50% total body surface area scald burns) for a period before the burn injuries and through the eighth day after the burn injuries. On the fifth day after the burn injuries, between 8 and 9 AM, control animals and animals with burns were given an intra-arterial dose of IL-6 polyclonal neutralizing antibody (IL-6 pAb) that was equivalent to one half of the neutralizing dose of IL-6 pAb. This calculation was based on plasma levels of IL-6 obtained from rats with burns in previous studies and on the neutralizing capability of the IL-6 used. On the sixth and seventh days after the burn injuries, a full neutralizing dose of IL-6 pAb was given. Blood samples were obtained for IL-6 assays at baseline and after treatment with IL-6 pAb but were lost because of the failure of an ultracold freezer. A one half neutralizing dose of IL-6 pAb produced no discernible effect on the body temperature of the control animals or of the animals with burns. On the sixth and seventh days after the burn injury, IL-6 pAb produced 45% and 34% respective decreases in body temperature compared with the animals with burns that received saline solution (P < .05 for both comparisons). On the eighth day after the burn injuries, the effect had completely dissipated. We concluded that our results support the idea that increased circulating levels of IL-6 may be causally related to fever that occurs in nonseptic rats with large burn wounds.