Interleukin-1 receptor antagonist inhibits endotoxin fever and systemic interleukin-6 induction in the rat
Interleukin-1 receptor antagonist inhibits endotoxin fever and systemic interleukin-6 induction in the rat
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DOI：
10.1152/ajpendo.1996.270.1.e91
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发表时间：
1996-01-01
影响因子：
5.1
通讯作者：
Hopkins, SJ
中科院分区：
文献类型：
--
作者：
Luheshi, G;Miller, AJ;Hopkins, SJ
尽管许多研究表明脂多糖 (LPS) 和/或白细胞介素 (IL)-1 的致热活性是通过 IL-6 的诱导介导的，但最近的证据表明发烧与循环 IL-6 之间存在分离，这一点受到了质疑。本研究通过使用人重组白细胞介素 1 受体拮抗剂 (IL-1ra) 重新审视了这种关系。向大鼠注射LPS（100μg/kg ip）引起的发热（2.0℃）在LPS后1和2小时给予IL-1ra（16 mg/kg ip）时显着抑制（P < 0.05）。血浆IL-6的升高先于发热反应1-1.5小时，尽管血浆和脑脊液（CSF）中生物活性IL-6的浓度在4小时时没有降低，但在单次注射IL-1ra（16 mg/kg ip）后，在2小时血浆和CSF中IL-6生物活性分别被抑制80%和70%。脑室内注射IL-1ra（200μg/大鼠）可抑制LPS发热，但不影响腹腔注射LPS后2或4小时测定的血浆IL-6生物活性。这些数据表明，外周IL-1在发烧的诱导和之前血浆IL-6的升高中发挥作用，并且大脑内的IL-1在LPS诱导发烧中也很重要。
Although a number of studies indicate that the pyrogenic activity of lipopolysaccharide (LPS) and/or interleukin (IL)-1 is mediated via induction of IL-6, this has been questioned by recent evidence demonstrating a dissociation between fever and circulating IL-6. The present study reexamines this relationship by use of human recombinant interleukin-1 receptor antagonist (IL-1ra). Injection of LPS (100 mu g/kg ip) into rats induced fever (2.0 degrees C) that was significantly inhibited (P < 0.05) when IL-1ra (16 mg/kg ip) was given 1 and 2 h after LPS. The rise in plasma IL-6 preceded the febrile response by 1-1.5 h and, although the concentrations of bioactive IL-6 in plasma and cerebrospinal fluid (CSF) were not reduced at 4 h, at 2 h plasma and CSF IL-6 bioactivity was inhibited by 80 and 70%, respectively, after a single injection of IL-1ra (16 mg/kg ip). Intracerebroventricular injection of IL-1ra (200 mu g/rat) inhibited LPS fever but did not affect the plasma IL-6 bioactivity measured 2 or 4 h after intraperitoneal LPS. These data show that peripheral IL-1 plays a part in the induction of both fever and the rise in plasma IL-6 that precedes it, and that IL-1 within the brain is also important in the induction of fever by LPS.