Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice.
Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice.
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发表时间：
2000
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通讯作者：
R. Bluthé;S. Layé;B. Michaud;C. Combe;R. Dantzer;P. Parnet
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作者：
R. Bluthé;S. Layé;B. Michaud;C. Combe;R. Dantzer;P. Parnet
白细胞介素-1 (IL-1) 在宿主对感染的反应过程中介导疾病症状。 IL-1 通过几种受体亚型发挥作用。为了评估 I 型 IL-1 受体 (IL-1RI) 在 IL-1 疾病诱导作用中的作用，将 IL-1β 和细胞因子诱导剂脂多糖给予 IL-1RI 缺陷小鼠 (IL-1RI-/-)。通过社交探索抑郁、厌食、不动和体重减轻来评估疾病。 IL-1RI-/-小鼠对腹膜内（2微克/小鼠）和脑室内（2纳克/小鼠）施用的IL-1β的疾病诱导作用具有抵抗力，但仍然对腹膜内（2.5微克/小鼠）和脑室内（3纳克/小鼠）施用的脂多糖完全有反应。 IL-1RI-/-小鼠对脂多糖的敏感性并不是由于IL-1以外的促炎细胞因子的脑表达较高，因为在治疗后1小时通过半定量逆转录酶聚合酶链反应测量时，脂多糖诱导的脑IL-1β、肿瘤坏死因子-α（TNF-α）和IL-6转录物的表达在IL-1RI-/-和对照小鼠中是相同的。通过脑室内注射可溶性 TNF 受体片段、TNF 结合蛋白（3.6 微克/小鼠）来阻断大脑中 TNF-α 的作用，减弱了腹膜内注射脂多糖（1 微克/小鼠）对 IL-1RI-/- 行为的抑制作用，但对对照小鼠没有影响。由于 IL-1RI-/- 小鼠对脑室内 TNF-α (50 ng) 的敏感性并不比对照小鼠更敏感，因此这些结果表明 IL-1RI 介导 IL-1 的疾病效应，并且当最后一种细胞因子缺乏时，TNF-α 只是替代 IL-1。
Interleukin-1 (IL-1) mediates symptoms of sickness during the host response to infection. IL-1 exerts its effects via several subtypes of receptors. To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL-1RI-/- mice were resistant to the sickness-inducing effects of IL-1beta administered intraperitoneally (2 microg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 microg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL-1RI-/- mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL-1, since lipopolysaccharide-induced expression of brain IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 transcripts were identical in IL-1RI-/- and control mice when measured by semiquantitative reverse-transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF-alpha action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 microg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 microg/mouse) on behaviour in IL-1RI-/- but not in control mice. Since IL-1RI-/- mice were not more sensitive to intracerebroventricularly TNF-alpha (50 ng) than control mice, these results indicate that IL-1RI mediates the sickness effect of IL-1 and that TNF-alpha simply replaces IL-1 when this last cytokine is deficient.