THE VAGUS NERVE IN THE THERMOREGULATORY RESPONSE TO SYSTEMIC INFLAMMATION

Experimentally, systemic inflammation induced by a bolus intravenous i njection of lipopolysaccharide (LPS) may be accompanied by three diffe rent thermoregulatory responses: monophasic fever (the typical respons e to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsk y, C. T. Simons, N. Sugimoto, and hi. Szekely. Am. J. Physiol. (Regula tory Integra tive Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulat ory response. Adult Wistar rats were vagotomized (or sham operated) an d had an intravenous catheter implanted. On day 28 postvagotomy, the t hermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 mu g/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major re sults were obtained. 1) In the sham-operated rats, the 1 mu g/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal coloni c temperature (T-c) rise of similar to 0.6 degrees C; this response wa s abated (no T-c changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 mu g/kg) were represen ted by biphasic fevers (the higher the dose, the less pronounced the f irst and the more pronounced the second phase was); none of these biph asic fevers was altered in the vagotomized animals. 3) In response to the 1,000 mu g/kg dose at 25 degrees C, hypothermia occurred: T-c chan ged by -0.5 +/- 0.1 degrees C (nadir); this hypothermia was exaggerate d(-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded tha t vagal afferentation may be important in the mediation of the respons e to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mecha nisms. This difference may be explained by the dose-dependent mechanis ms of the processing of exogenous pyrogens. Vagotomized animals also a ppear to be more sensitive to the hypothermizing action of LPS in a co ol environment; the mechanisms of this phenomenon remain speculative.