IL-6 and IL-1β in fever -: Studies using cytokine-deficient (knockout) mice
IL-6 and IL-1β in fever -: Studies using cytokine-deficient (knockout) mice
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DOI：
10.1111/j.1749-6632.1998.tb08310.x
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发表时间：
1998-01-01
期刊：
影响因子：
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通讯作者：
Zheng, H
中科院分区：
文献类型：
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作者：
Kozak, W;Kluger, MJ;Zheng, H
先前的数据支持这样的假设：在炎症过程中，白细胞介素 (IL)-1β 和 IL-6 参与发烧、下丘脑-垂体-肾上腺 (HPA) 轴的激活以及类二十烷酸的诱导。 IL-1β和IL-6的大部分病理生理作用由前列腺素（PG）介导，受其他细胞因子调节，并被糖皮质激素（GC）（HPA轴的最终产物）拮抗。为了进一步测试这些关系，我们在注射脂多糖（LPS）诱导全身炎症或注射松节油诱导局部脓肿后，使用生物遥测技术测量了IL-1β和/或IL-6基因缺陷（IL-1β敲除[KO]和IL-6KO）小鼠的体温变化。治疗后测量这些小鼠的循环 IL-6、肿瘤坏死因子 α (TNF-α)、GC 和 PGE。 IL-1 β KO 小鼠对高剂量 LPS 的反应是发烧减少，而 IL-6 KO 小鼠则发烧正常。相比之下，两种类型的 RO 小鼠都不会因松节油而发烧。在注射松节油的两种类型的 RO 小鼠中，PGE 水平（在循环中测量）均受到抑制。 IL-1β KO 小鼠在注射松节油后显示出 IG6 缺陷，但注射 LPS 后则没有。 LPS 诱导的 TNF-α 增加在 IL-1 β KO 小鼠和野生型小鼠之间没有差异，而 IL-6 KO 小鼠表现出 LPS 诱导的循环 TNF-α 加剧。注射 LPS 或松节油后，RO 和野生型小鼠的血浆 GC 升高没有差异，表明炎症期间激活 HPA 轴不需要 IF-1 β 和 IL-6。我们的数据表明，在小鼠中，IL-1β和IL-6对于局部炎症期间引起发烧至关重要，而在全身炎症中它们似乎仅导致发烧。
Previous data support the hypothesis that during inflammation, interleukin (IL)-1 beta and IL-6 are involved in fever, in activation of the hypothalamic-pituitary-adrenal (HPA) axis, and in the induction of eicosanoids. Most of the pathophysiologic effects of IL-1 beta and IL-6 are mediated by prostaglandins (PGs), modulated by other cytokines, and antagonized by glucocorticoids (GC), a final product of the HPA axis. To further test these relationships, we measured changes in body temperature using biotelemetry in mice deficient in genes for IL-1 beta and/or IL-6 (IL-1 beta knockout [KO] and IL-6 KO) following injection with lipopolysaccharide (LPS) to induce systemic inflammation or turpentine to induce local abscess. Circulating IL-6, tumor necrosis factor alpha (TNF-alpha), GC, and PGE, were measured in these mice after treatment. IL-1 beta KO mice responded with reduced fever and IL-6 KO mice with normal fever to a high dose of LPS. In contrast, neither type of RO mice produced fever to turpentine. PGE, levels (measured in the circulation) were suppressed in both types of RO mice injected with turpentine. IL-1 beta KO mice showed deficiency in IG6 following turpentine, but not LPS, injection. LPS-induced increases in TNF-a did not differ between IL-1 beta KO mice and their wild-type counterparts, whereas IL-6 KO mice showed exacerbated LPS-induced circulating TNF-alpha. No differences were noted in plasma elevations of GC between RO and wild-type mice following injection of LPS or turpentine, indicating that IF-1 beta and IL-6 are not required for activation of the HPA axis during inflammation. Our data demonstrate that in the mouse, IL-1 beta and IL-6 are critical for the induction of fever during local inflammation, whereas in systemic inflammation they appear only to contribute to fever.