Roth J, De Souza G E
Department of Veterinary Physiology, School of Veterinary Medicine, University of Giessen, Giessen, Germany.
Braz J Med Biol Res. 2001 Mar;34(3):301-14. doi: 10.1590/s0100-879x2001000300003.
The immune and central nervous systems are functionally connected and interacting. The concept that the immune signaling to the brain which induces fever during infection and inflammation is mediated by circulating cytokines has been traditionally accepted. Administration of bacterial lipopolysaccharide (LPS) induces the appearance of a so-termed "cytokine cascade" in the circulation more or less concomitantly to the developing febrile response. Also, LPS-like fever can be induced by systemic administration of key cytokines (IL-1 beta, TNF-alpha, and others). However, anti-cytokine strategies against IL-1 beta or TNF-alpha along with systemic injections of LPS frequently lead to attenuation of the later stages of the febrile response but not of the initial phase of fever, indicating that cytokines are rather involved in the maintenance than in the early induction of fever. Within the last years experimental evidence has accumulated indicating the existence of neural transport pathways of immune signals to the brain. Because subdiaphragmatic vagotomy prevents or attenuates fever in response to intraperitoneal or intravenous injections of LPS, a role for vagal afferent nerve fibers in fever induction has been proposed. Also other sensory nerves may participate in the manifestation of febrile responses under certain experimental conditions. Thus, injection of a small dose of LPS into an artificial subcutaneous chamber results in fever and formation of cytokines within the inflamed tissue around the site of injection. This febrile response can be blocked in part by injection of a local anesthetic into the subcutaneous chamber, indicating a participation of cutaneous afferent nerve signals in the manifestation of fever in this model. In conclusion, humoral signals and an inflammatory stimulation of afferent sensory nerves can participate in the generation and maintenance of a febrile response.
免疫和中枢神经系统在功能上相互连接并相互作用。传统上认为，感染和炎症期间诱导发热的免疫信号向大脑的传递是由循环细胞因子介导的。给予细菌脂多糖（LPS）或多或少会在发热反应出现的同时，在循环中诱导出所谓的“细胞因子级联反应”。此外，全身注射关键细胞因子（IL-1β、TNF-α等）也可诱导类似LPS的发热。然而，针对IL-1β或TNF-α的抗细胞因子策略以及全身注射LPS，常常导致发热反应后期的减弱，而非发热初期的减弱，这表明细胞因子更多地参与发热的维持而非早期诱导。在过去几年中，积累的实验证据表明存在免疫信号向大脑的神经传输途径。由于膈下迷走神经切断术可预防或减弱对腹腔内或静脉注射LPS的发热反应，因此有人提出迷走神经传入纤维在发热诱导中发挥作用。在某些实验条件下，其他感觉神经也可能参与发热反应的表现。因此，向人工皮下腔室注射小剂量LPS会导致发热，并在注射部位周围的炎症组织中形成细胞因子。通过向皮下腔室注射局部麻醉剂，这种发热反应可部分被阻断，这表明皮肤传入神经信号参与了该模型中发热的表现。总之，体液信号和传入感觉神经的炎症刺激可参与发热反应的产生和维持。
