Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease.
Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease.
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DOI：
10.1182/blood.v79.9.2196.2196
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发表时间：
1992-05
期刊：
影响因子：
20.3
通讯作者：
E. Fischer;K. J. V. Zee;Michael A. Marano;C. S. Rock;John S. Kenney;D. Poutsiaka;C. A. Dinarello;Stephen F. Lowry;L. Moldawer
中科院分区：
文献类型：
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作者：
E. Fischer;K. J. V. Zee;Michael A. Marano;C. S. Rock;John S. Kenney;D. Poutsiaka;C. A. Dinarello;Stephen F. Lowry;L. Moldawer
白细胞介素-1受体拮抗剂（IL-1 ra）是一种22-Kd的蛋白质，与IL-1 β具有同源性，与IL-1受体结合，但没有已知的激动剂特性。这种抑制剂似乎是第一种细胞因子，其唯一功能是阻断另一种细胞因子的作用。外源性IL-1 ra给药已被证明可以降低实验性脓毒性休克的死亡率。我们现在报道IL-1 ra是内源性产生的，并在实验性炎症和临床疾病中循环。在人类志愿者实验性内毒素血症后，IL-1 ra浓度从基线浓度460 +/- 200 pg mL-1增加至3小时的14，870 +/- 290 pg mL-1（P <0.05）。在重症患者的所有血浆样本中也可检测到IL-1 ra，平均浓度为8，680 +/-2，060 pg mL-1（范围为320至55，370 pg mL-1）。在非人灵长类动物中，大肠杆菌感染性休克诱导血浆IL-4 ra水平升高（P <0.05）。然而，在最终死于感染性休克的动物中，IL-1 ra的量被认为不足以阻断与高IL-1 β水平相关的病理性后遗症。研究结果表明，IL-1 ra可能通过改变细胞因子及其拮抗剂之间的平衡，在调节全身宿主对各种非致死性疾病状态的反应中发挥作用。
Interleukin-1 receptor antagonist (IL-1ra) is a 22-Kd protein that shares homology with IL-1 beta, binds to the IL-1 receptor, but has no known agonist properties. This inhibitor appears to be the first cytokine whose sole function is to block the actions of another cytokine. Exogenous IL-1ra administration has been shown to reduce mortality in experimental septic shock. We now report that IL-1ra is endogenously produced and circulates in experimental inflammation and in clinical disease. After experimental endotoxemia in human volunteers, IL-1ra concentrations increase from a baseline concentration of 460 +/- 200 pg mL-1 to 14,870 +/- 290 pg mL-1 at 3 hours (P less than .05). IL-1ra is also detectable in all plasma samples from critically ill patients with a mean concentration of 8,680 +/- 2,060 pg mL-1 (range 320 to 55,370 pgs mL-1). In nonhuman primates, Escherichia coli septic shock induces elevated plasma levels of IL-4ra (P less than .05). However, in animals that eventually succumb to septic shock, Il-1ra appears in quantities presumed inadequate to block the pathologic sequelae associated with high IL-1 beta levels. The findings suggest that IL-1ra may play a role in modulating the systemic host responses to a variety of nonlethal disease states by altering the balance between cytokines and their antagonists.