DIFFERENT RECEPTOR MECHANISMS MEDIATE THE PYROGENIC AND BEHAVIORAL-EFFECTS OF INTERLEUKIN-1
DIFFERENT RECEPTOR MECHANISMS MEDIATE THE PYROGENIC AND BEHAVIORAL-EFFECTS OF INTERLEUKIN-1
复制标题
DOI：
10.1073/pnas.89.19.9117
复制
发表时间：
1992-10-01
影响因子：
11.1
通讯作者：
VANNICE, JL
中科院分区：
文献类型：
--
作者：
KENT, S;BLUTHE, RM;VANNICE, JL
白细胞介素 1 (IL-1) 是免疫激活过程中释放的细胞因子，介导宿主对感染和炎症的反应。外周和中枢注射 IL-1 会引起发烧和疾病行为，包括进食动机降低和社交活动兴趣降低。为了确定导致这些作用的受体机制，给大鼠注射了 IL-1 受体拮抗剂 (IL-1ra)，这是一种内源性细胞因子，可作为 IL-1 受体的纯拮抗剂。仅当两种细胞因子均腹腔注射时，IL-1ra 才能阻止注射重组人 IL-1 引起的体温和耗氧量增加。相比之下，ip。当通过与拮抗剂相同的途径施用IL-1ra时，脑室内施用IL-1ra可阻断IL-1β对食物驱动行为和社会探索的抑制作用。此外，脑室内 IL-1ra 阻断了腹膜内注射产生的社会探索的减少。 IL-1beta 但对腹膜内注射引起的食物驱动行为的减少仅具有部分拮抗作用。 IL-1β。在每种情况下，IL-1ra的剂量均超过IL-1的生物活性剂量的100至100倍。这些结果表明介导 IL-1 的行为和热原作用的受体机制是异质的。
Interleukin 1 (IL-1) is a cytokine released during immune activation that mediates the host's response to infection and inflammation. Peripheral and central injections of IL-1 induce fever and sickness behavior, including decreased food motivation and reduced interest in social activities. To determine the receptor mechanisms responsible for these effects, rats were injected with IL-1 receptor antagonist (IL-1ra), an endogenous cytokine that acts as a pure antagonist of IL-1 receptors. IL-1ra blocked the increased body temperature and oxygen consumption induced by injection of recombinant human IL-1 only when both cytokines were administered i.p. In contrast, i.p. or intracerebroventricular administration of IL-1ra blocked the depressive effect of IL-1beta on food-motivated behavior and social exploration when this cytokine was administered by the same route as the antagonist. In addition, intracerebroventricular IL-1ra blocked the reduction in social exploration produced by i.p. IL-1beta but had only partial antagonist effects on the decrease in food-motivated behavior induced by i.p. IL-1beta. In each case, the dose of IL-1ra was 100- to 100-fold in excess of the biologically active dose of IL-1. These results suggest that the receptor mechanisms that mediate the behavioral and pyrogenic effects of IL-1 are heterogeneous.