Humoral versus neural pathways for fever production in rats after administration of lipopolysaccharide

These studies address the question of the relative roles of humoral and neural pathways in the genesis and control of the fever component of the acute phase response.

Two experiments were performed to examine the effect of vagotomy (VagX) on the febrile response to intraperitoneal (i.p.) and intra-arterial (i.a.) lipopolysaccharide (LPS), and plasma cytokine and LPS concentrations after intravenous (i.v.) or i.p. injections of LPS. In experiment 1, body temperature (T(B)) was obtained from unperturbed animals by using radio transmitters and telemetry after injection of LPS i.a. or i.p. In the second study, serial blood samples were obtained for cytokine and LPS assay after injection of LPS either i.v. or i.p. Colonic temperatures (T(C)) were obtained from indwelling thermistors.

The maximal increments in T(B) for animals receiving LPS i.a. and i.p. with or without VagX were not different from one another: sham vagotomy (Sham-VagX) + LPS i.a., 1.20 +/- 0.26 degrees C; VagX + LPS i.a., 1.23 +/- 0.64 degrees C; Sham-VagX + LPS i.p., 1.45 +/- 0.27 degrees C; VagX + LPS i.p., 1.50 +/- 0.35 degrees C (F = 1.12, p = 0.36). Neither were the four resulting response curves for T(B) different from one another. Plasma levels of LPS, tumor necrosis factor-alpha, and interleukin-6 were significantly elevated at 45 minutes after LPS injection by either the i.v. or i.p. routes, preceding any increments in T(B), and were not effected by VagX.

Fever development for animals receiving LPS in experiment 1 demonstrates a temporal relationship -- with increments in plasma levels of LPS and pyrogenic cytokines obtained in experiment 2 after administration of LPS either i.p. or i.v. Vagotomy had no discernible effect on the responses regardless of the route of administration of LPS.