Klir J J, McClellan J L, Kluger M J
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
Am J Physiol. 1994 Jun;266(6 Pt 2):R1845-8. doi: 10.1152/ajpregu.1994.266.6.R1845.
The purpose of this study was to determine, using push-pull perfusion, whether the central pyrogenic action of interleukin-6 (IL-6) during lipopolysaccharide (LPS)-induced fever in rats is induced by interleukin-1 beta (IL-1 beta) and to determine the source of the hypothalamic IL-6 (i.e., from the periphery or from the brain). Samples of cerebrospinal fluid were collected 60 min before and 60, 120, 180, and 240 min after the intraperitoneal injection of LPS or saline as a control. Immediately before the injection of LPS, anti-rat neutralizing IL-1 beta antibody (anti-IL-1 beta) or control immunoglobulin G antibody (IgG) was microinjected into the anterior hypothalamus (AH) of each rat. At the end of the last perfusion, blood was collected by cardiac puncture. Microinjection of anti-IL-1 beta into the AH caused a 58% reduction of LPS fever (measured by biotelemetry). AH microinjection of anti-IL-1 beta or IgG followed by intraperitoneal injection of saline did not result in significant change in core body temperature. AH injection of anti-IL-1 beta also resulted in a 97% reduction in AH IL-6 levels during LPS fever, with the average values of IL-6 for the four post-LPS time points being 113 +/- 50 U/ml for the rats injected with IgG and LPS and 3 +/- 2 U/ml for the rats injected with anti-IL-1 beta and LPS (P = 0.024).(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是利用推挽式灌注法，确定在大鼠脂多糖（LPS）诱导发热过程中，白细胞介素-6（IL-6）的中枢致热作用是否由白细胞介素-1β（IL-1β）诱导，并确定下丘脑IL-6的来源（即来自外周还是大脑）。在腹腔注射LPS或作为对照的生理盐水之前60分钟以及之后60、120、180和240分钟收集脑脊液样本。在注射LPS之前，将抗大鼠中和IL-1β抗体（抗IL-1β）或对照免疫球蛋白G抗体（IgG）微量注射到每只大鼠的下丘脑前部（AH）。在最后一次灌注结束时，通过心脏穿刺采集血液。向AH微量注射抗IL-1β可使LPS发热降低58%（通过生物遥测测量）。AH微量注射抗IL-1β或IgG后腹腔注射生理盐水，并未导致核心体温出现显著变化。AH注射抗IL-1β还导致LPS发热期间AH中IL-6水平降低97%，LPS注射后四个时间点的IL-6平均值，注射IgG和LPS的大鼠为113±50 U/ml，注射抗IL-1β和LPS的大鼠为3±2 U/ml（P = 0.024）。（摘要截断于250字）
