Nakamori T, Morimoto A, Yamaguchi K, Watanabe T, Murakami N
Department of Physiology, Yamaguchi University School of Medicine, Japan.
J Physiol. 1994 Apr 1;476(1):177-86.
Interleukin-1 beta (IL-1 beta) production in the brain and the spleen was investigated in rabbits made febrile by intravenous (I.V.) injection of endotoxin, or human recombinant IL-1 beta (hIL-1 beta). The endotoxin used in the present study was the lipopolysaccharide (LPS) of Salmonella typhosa endotoxin. Monophasic fever was induced by I.V. injection of a low dose of LPS (0.02 micrograms kg-1) and biphasic fever by I.V. injection of a large dose of LPS (4 micrograms kg-1), a sublethal dose of LPS (40 micrograms kg-1) or hIL-1 beta (2 micrograms kg-1). In situ hybridization and immunohistochemical studies revealed that, although no IL-1 beta production was observed in the brain at 1 and 3 h after injection of a low dose of LPS (0.02 micrograms kg-1) or of hIL-1 beta (2 micrograms kg-1), IL-1 beta production was demonstrated in organum vasculosum laminae terminalis (OVLT) and some cells around the blood vessels in the parenchyma 1 h after 4 micrograms kg-1 LPS. IL-1 beta production was detected throughout the brain after 40 micrograms kg-1 LPS. Pretreatment with indomethacin, an inhibitor of prostaglandin synthesis, did not affect IL-1 beta production in the brain induced by 4 micrograms kg-1 LPS. The cell type which produces IL-1 beta in the OVLT following LPS injection was confirmed to be a macrophage by electron microscopy. The cells producing IL-1 beta in the parenchyma were determined to be microglial cells. In the spleen, each dose of LPS induced a significant increase in IL-1 beta production in polymorphonuclear cells and macrophages in the red pulp 1 h after injection. However, 2 micrograms kg-1 hIL-1 beta did not induce IL-1 beta production in the spleen. The present results show clearly that systemic administration of LPS induces IL-1 beta production in the OVLT which may be responsible for induction of the second phase of biphasic fever. The production of IL-1 beta in the OVLT was not attributable to the action of peripherally synthesized IL-1 beta or prostaglandins.
通过静脉注射内毒素或重组人白细胞介素 -1β（hIL-1β）使家兔发热，研究其脑和脾中白细胞介素 -1β（IL-1β）的产生情况。本研究中使用的内毒素是伤寒沙门氏菌内毒素的脂多糖（LPS）。静脉注射低剂量LPS（0.02微克/千克）可诱导单相热，静脉注射大剂量LPS（4微克/千克）、亚致死剂量LPS（40微克/千克）或hIL-1β（2微克/千克）可诱导双相热。原位杂交和免疫组织化学研究显示，尽管在注射低剂量LPS（0.02微克/千克）或hIL-1β（2微克/千克）后1小时和3小时，脑中未观察到IL-1β的产生，但在注射4微克/千克LPS后1小时，终板血管器（OVLT）和实质内血管周围的一些细胞中显示有IL-1β的产生。注射40微克/千克LPS后，全脑均检测到IL-1β的产生。用前列腺素合成抑制剂吲哚美辛预处理，不影响4微克/千克LPS诱导的脑中IL-1β的产生。通过电子显微镜证实，LPS注射后OVLT中产生IL-1β的细胞类型为巨噬细胞。实质中产生IL-1β的细胞被确定为小胶质细胞。在脾脏中，各剂量的LPS在注射后1小时均诱导红髓中多形核细胞和巨噬细胞的IL-1β产生显著增加。然而，2微克/千克的hIL-1β未诱导脾脏中IL-1β的产生。目前的结果清楚地表明，全身给予LPS可诱导OVLT中IL-1β的产生，这可能是双相热第二阶段诱导的原因。OVLT中IL-1β的产生不归因于外周合成的IL-1β或前列腺素的作用。
