Hansen M K, O'Connor K A, Goehler L E, Watkins L R, Maier S F
Department of Psychology and Center for Neuroscience, University of Colorado at Boulder, Boulder, CO 80309, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 Apr;280(4):R929-34. doi: 10.1152/ajpregu.2001.280.4.R929.
It has been suggested that proinflammatory cytokines communicate to the brain via a neural pathway involving activation of vagal afferents by interleukin-1beta (IL-1beta), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy blocks IL-1beta-induced, brain-mediated responses such as fever. However, vagotomy has also been reported to be ineffective. Neural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities of cytokine would become systemic. Here, we examined core body temperature after intraperitoneal injections of three doses of recombinat human IL-1beta (rh-IL-1beta). Subdiaphragmatic vagotomy completely blocked the fever produced by 0.1 microg/kg, only partially blocked the fever produced by 0.5 microg/kg, and had no effect at all on the fever that followed 1.0 microg/kg rh-IL-1beta. Blood levels of rh-IL-1beta did not become greater than normal basal levels of endogenous rat IL-beta until the 0.5-microg/kg dose nor was IL-1beta induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1beta induce fever via a vagal route and that dose may account for some of the discrepancies in the literature.
有人提出，促炎细胞因子除了通过血行途径外，还可通过一条神经通路与大脑进行沟通，该神经通路涉及白细胞介素-1β（IL-1β）激活迷走神经传入纤维。作为支持证据，膈下迷走神经切断术可阻断IL-1β诱导的大脑介导反应，如发热。然而，也有报道称迷走神经切断术无效。当可能发生局部作用但只有极少量细胞因子进入全身循环时，神经信号传导在低剂量细胞因子作用下可能尤为重要。在此，我们检测了腹腔注射三种剂量重组人IL-1β（rh-IL-1β）后机体核心体温。膈下迷走神经切断术完全阻断了0.1微克/千克剂量rh-IL-1β引起的发热，仅部分阻断了0.5微克/千克剂量引起的发热，而对1.0微克/千克rh-IL-1β引起的发热则完全没有影响。直到0.5微克/千克剂量时，rh-IL-1β的血药浓度才超过内源性大鼠IL-β的正常基础水平，垂体中IL-1β也是直到该剂量才被诱导产生。这些结果表明，低剂量腹腔注射IL-1β通过迷走神经途径诱导发热，这一剂量可能解释了文献中的一些差异。
