INTERLEUKIN-1 INDUCES A SHOCK-LIKE STATE IN RABBITS - SYNERGISM WITH TUMOR NECROSIS FACTOR AND THE EFFECT OF CYCLOOXYGENASE INHIBITION
INTERLEUKIN-1 INDUCES A SHOCK-LIKE STATE IN RABBITS - SYNERGISM WITH TUMOR NECROSIS FACTOR AND THE EFFECT OF CYCLOOXYGENASE INHIBITION
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DOI：
10.1172/jci113431
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发表时间：
1988-04-01
影响因子：
15.9
通讯作者：
DINARELLO, CA
中科院分区：
文献类型：
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作者：
OKUSAWA, S;GELFAND, JA;DINARELLO, CA
除了激活T和B淋巴细胞外，白细胞介素1（IL-1）还诱导宿主对感染和损伤的典型反应的几种血液学和代谢变化。我们现在报告一个新的生物学特性，即诱导低血压。给予重组人IL-1-β（5 μ g/kg）的单次静脉内注射的兔迅速发展为降低的全身动脉压，其在50-60分钟后达到最低水平，并在3小时后缓慢恢复到IL-1前的值。伴随低血压，全身血管阻力和中心静脉压下降，心输出量和心率增加。在IL-1前15分钟给予布洛芬可预防这些反应。推注IL-1，然后2小时输注持续低血压，并与白细胞减少症和血小板减少症。IL-1前15分钟给予IL-1。推注IL-1后2小时输注可维持低血压，并伴有白细胞减少和血小板减少。在输注中点给予Ithalazone可逆转所有血流动力学参数的变化，但对白细胞减少症或血小板减少症无影响。肿瘤坏死因子（TNF）也诱导休克样状态的兔子。当IL-1或TNF的剂量降低至1 μ g/kg时，没有观察到血液动力学变化;然而，这两种细胞因子的低剂量组合导致严重的休克样状态，包括严重肺水肿和出血的组织学证据。布洛芬预处理可预防低剂量细胞因子联合诱导的血液动力学、白细胞和血小板变化，并改善肺组织损伤。这些结果表明，IL-1，像TNF一样，具有诱导脓毒性休克典型的血液动力学和血液学变化的能力，并且IL-1和TNF的组合比单独的任一药剂更有效。这些作用似乎需要环氧合酶产品，并表明静脉内环氧合酶抑制剂可能是治疗IL-1/TNF介导的休克患者的价值。
In addition to activating T and B lymphocytes, interleukin 1 (IL-1) induces several hematologic and metabolic changes typical of host responses to infection and injury. We now report a new biological property, namely, the induction of hypotension. Rabbits given a single intravenous injection of recombinant human IL-1-beta (5 .mu.g/kg) rapidly developed decreased systemic arterial pressure, which reached the lowest levels after 50-60 min and slowly returned to pre-IL-1 values after 3 h. Associated with the hypotension, systemic vascular resistance and central venous pressure fell, while cardiac output and heart rate increased. These responses were prevented by ibuprofen given 15 min before the IL-1. A bolus injection of IL-1 followed by a 2-h infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given 15 min before the IL-1. A bolus injectionof IL-1 followed by a 2-h infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given at the mid-point of the infusion reversed the changes in all hemodynamic parameters, but had no effect on the leukopenia or thrombocytopenia. Tumor necrosis factor (TNF)also induced a shock-like state in rabbits. When the dose of IL-1 or TNF was reduced to 1 .mu.g/kg, no hemodynamic changes were observed; however, the combination of these low doses of both cytokines resulted in a profound shock-like state including histological evidence of severe pulmonary edema and hemorrhage. Pretreatment with ibuprofen prevented the hemodynamic, leukocyte, and platelet changes induced by the low-dose cytokine combination, and ameliorated the pulmonary tissue damage. These results demonstrate that IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, and that the combination of IL-1 and TNF is more potent than either agent alone. These effects seem to require cyclooxygenase products, and suggest that intravenous cyclooxygenase inhibitors may be of therapeutic value in patients with IL-1/TNF-mediated shock.