LeMay L G, Otterness I G, Vander A J, Kluger M J
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
Cytokine. 1990 May;2(3):199-204. doi: 10.1016/1043-4666(90)90016-m.
Although it has often been speculated that Interleukin (IL) 1 alpha and IL 1 beta are circulating endogenous pyrogens (EP), there are few data demonstrating an elevation of these cytokines in the plasma of febrile animals. We hypothesized that IL 1 is released locally and may act to stimulate the release of another pyrogen, IL 6, which circulates to the brain to cause fever. The major purpose of the present study was to determine whether pretreatment of rats with antiserum to IL 1 beta, which attenuates lipopolysaccharide (LPS) induced fever, also results in an attenuation of the rise in plasma and cerebrospinal fluid (CSF) concentrations of IL 6. Our results show that injection of IL 1 beta produced dose-dependent rises in temperature and increases in plasma and CSF IL 6 activity, and that pretreatment of rats i.v. with antiserum to IL 1 beta produced a 55% decrease in the fever caused by LPS injection, a 68% decrease in plasma IL 6, and a 67% decrease in CSF IL 6. These data confirm the findings of previous studies that IL 1 beta is required for a portion of LPS-induced fever and also provide the first in vivo demonstration that the rise of IL 6 in rats injected with a fever-inducing dose of LPS can be significantly blocked by antiserum to IL 1 beta. Overall, the data in our study can be interpreted as being consistent with the hypothesis that the pyrogenic effect of IL 1 beta is mediated mainly through the release of IL 6, but conclusive confirmation of this hypothesis must await studies with antibodies to IL 6.
尽管人们常常推测白细胞介素（IL）-1α和IL-1β是循环内源性致热原（EP），但几乎没有数据表明这些细胞因子在发热动物的血浆中升高。我们推测IL-1是在局部释放的，可能会刺激另一种致热原IL-6的释放，IL-6会循环至大脑引起发热。本研究的主要目的是确定用抗IL-1β抗血清预处理大鼠（该抗血清可减弱脂多糖（LPS）诱导的发热）是否也会导致血浆和脑脊液（CSF）中IL-6浓度的升高减弱。我们的结果表明，注射IL-1β会导致体温呈剂量依赖性升高，血浆和CSF中IL-6活性增加，并且静脉注射抗IL-1β抗血清预处理大鼠可使LPS注射引起的发热降低55%，血浆IL-6降低68%，CSF IL-6降低67%。这些数据证实了先前研究的结果，即一部分LPS诱导的发热需要IL-1β，并且还首次在体内证明，注射致热剂量LPS的大鼠中IL-6的升高可被抗IL-1β抗血清显著阻断。总体而言，我们研究中的数据可以解释为与以下假设一致，即IL-1β的致热作用主要是通过IL-6的释放介导的，但这一假设的确凿证实必须等待针对IL-6抗体的研究。
