Bastos-Pereira Amanda L, Fraga Daniel, Ott Daniela, Simm Björn, Murgott Jolanta, Roth Joachim, Zampronio Aleksander R
Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
J Appl Physiol (1985). 2014 May 1;116(9):1220-9. doi: 10.1152/japplphysiol.01278.2013. Epub 2014 Mar 20.
This study compared the involvement of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) within the central nervous system (CNS) in the febrile response induced by zymosan (zym) and lipopolysaccharide (LPS). In addition, we investigated whether zym could activate important regions related to fever; namely, the vascular organ of the laminae terminalis (OVLT) and the median preoptic nucleus (MnPO). Intraperitoneal injection of zym (1, 3, and 10 mg/kg) induced a dose-related increase in core temperature. Zym (3 mg/kg) also reduced tail skin temperature, suggesting the activation of heat conservation mechanisms, as expected, during fever. LPS increased plasma levels of TNF-α measured at 1 h, IL-1β measured at 2 h, and IL-6 measured at 3 h after injection. Zym increased circulating levels of IL-6 but not those of TNF-α or IL-1β at the same time points. In addition, an intracerebroventricular injection of antibodies against TNF-α (2.5 μg) and IL-6 (10 μg) or the IL-1 receptor antagonist (160 ng) reduced the febrile response induced by zym and LPS. Zym (100 μg/ml) also increased intracellular calcium concentration in the OVLT and MnPO from rat primary neuroglial cultures and increased release of TNF-α and IL-6 into the supernatants of these cultures. Together, these results suggest that TNF-α, IL-1β, and IL-6 within the CNS participate in the febrile response induced by zym. However, the time course of release of these cytokines may be different from that of LPS. In addition, zym can directly activate the brain areas related to fever.
本研究比较了中枢神经系统（CNS）中白细胞介素-1β（IL-1β）、IL-6和肿瘤坏死因子-α（TNF-α）在酵母聚糖（zym）和脂多糖（LPS）诱导的发热反应中的参与情况。此外，我们研究了zym是否能激活与发热相关的重要区域，即终板血管器（OVLT）和视前正中核（MnPO）。腹腔注射zym（1、3和10 mg/kg）引起核心温度呈剂量相关的升高。如预期的那样，在发热期间，zym（3 mg/kg）还降低了尾部皮肤温度，提示产热机制被激活。LPS在注射后1小时使血浆TNF-α水平升高，2小时使IL-1β水平升高，3小时使IL-6水平升高。在相同时间点，zym使循环中的IL-6水平升高，但未使TNF-α或IL-1β水平升高。此外，脑室内注射抗TNF-α（2.5 μg）和IL-6（10 μg）的抗体或白细胞介素-1受体拮抗剂（160 ng）可降低zym和LPS诱导的发热反应。zym（100 μg/ml）还使大鼠原代神经胶质细胞培养物中OVLT和MnPO的细胞内钙浓度升高，并使这些培养物上清液中TNF-α和IL-6的释放增加。总之，这些结果表明，CNS中的TNF-α、IL-1β和IL-6参与了zym诱导的发热反应。然而，这些细胞因子的释放时间进程可能与LPS不同。此外，zym可直接激活与发热相关的脑区。
