Plaza M A, Fioramonti J, Bueno L
Department of Pharmacology, INRA, Toulouse, France.
Dig Dis Sci. 1997 Feb;42(2):242-50. doi: 10.1023/a:1018837112572.
Cytokines are involved in the symptoms of the acute phase response induced by infectious diseases in humans as well as in animals, and interleukin-1 beta (IL-1 beta) has a pivotal role in these changes. The role of central IL-1 beta in the gastrointestinal hypomotility and fever evoked by intravenous administration of lipopolysaccharide (LPS) and the mechanisms involved, were investigated in sheep as an experimental model. LPS (0.1 microgram/kg, intravenously) induced gastrointestinal hypomotility and fever that were significantly reduced by prior intracerebroventricular administration of IL-1 receptor antagonist protein (IL-1ra, 2 micrograms/kg). The effects of LPS were mimicked by intracerebroventricular IL-1 beta (50 ng/kg), whereas IL-1 beta injected intravenously at the same dose only caused a slight and transient fever without modifying the gastrointestinal motility. Prior intracerebroventricular administration of the cyclooxygenase inhibitor indomethacin (100 micrograms/kg) but not the corticotropin-releasing factor (CRF) receptor antagonist alpha-helical CRF9-41 (5 micrograms/kg) blocked all effects by both LPS and IL-1 beta. These results suggest that in sheep, LPS induces digestive motor disturbances through a central release of IL-1 beta and prostaglandins.
细胞因子参与人类和动物因传染病引发的急性期反应症状，而白细胞介素-1β（IL-1β）在这些变化中起关键作用。以绵羊作为实验模型，研究了中枢IL-1β在静脉注射脂多糖（LPS）诱发的胃肠动力减弱和发热中的作用及其相关机制。静脉注射LPS（0.1微克/千克）可诱发胃肠动力减弱和发热，预先脑室内注射IL-1受体拮抗剂蛋白（IL-1ra，2微克/千克）可使其显著减轻。脑室内注射IL-1β（50纳克/千克）可模拟LPS的作用，而静脉注射相同剂量的IL-1β仅引起轻微短暂的发热，且不改变胃肠动力。预先脑室内注射环氧化酶抑制剂吲哚美辛（100微克/千克）而非促肾上腺皮质激素释放因子（CRF）受体拮抗剂α-螺旋CRF9-41（5微克/千克）可阻断LPS和IL-1β的所有作用。这些结果表明，在绵羊中，LPS通过中枢释放IL-1β和前列腺素诱导消化运动障碍。
