INTERLEUKIN-1 RECEPTOR BLOCKADE ATTENUATES THE HOST INFLAMMATORY RESPONSE
INTERLEUKIN-1 RECEPTOR BLOCKADE ATTENUATES THE HOST INFLAMMATORY RESPONSE
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DOI：
10.1073/pnas.87.13.4966
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发表时间：
1990-07-01
影响因子：
11.1
通讯作者：
MOLDAWER, LL
中科院分区：
文献类型：
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作者：
GERSHENWALD, JE;FONG, Y;MOLDAWER, LL
细胞因子，包括白介素1(IL-1)、肿瘤坏死因子α和白介素6，通常是在组织损伤时产生的，并有助于几种宿主的反应，如体重减轻、厌食和急性期蛋白质合成。然而，IL-1在特定组织反应中的作用尚不清楚。为了验证我们的假设，即在体内特异性阻断IL-1‘’S的作用可能会抑制与炎症相关的分解代谢宿主变化，在松节油诱导的不孕脓肿开始之前，用针对小鼠IL-1受体的单抗被动免疫小鼠。该抗体通过抑制IL-1α，在体外阻止IL-1介导的小鼠胸腺细胞的增殖。和IL-1β。通过竞争共同的受体。每日注射抗IL-1受体单抗Ig G可预防松节油攻击后的体重减轻。体成分分析证实，被动免疫保存了仔猪的瘦肉组织和脂肪。此外，使用抗IL-1受体的单抗可显著减弱血浆淀粉样蛋白P和白细胞介素6的反应，但不影响血浆白蛋白的下降或循环皮质酮的增加。用针对另一种细胞因子肿瘤坏死因子α的多克隆抗血清被动免疫类似的小鼠，既不能防止体重减轻，也不能阻止在这种炎症模型中观察到的肝脏急性时相蛋白的变化。这些发现表明，IL-1在炎症过程中协调体重减轻和身体成分变化，并有助于诱导白细胞介素6和急性期蛋白质合成。
Cytokines, including interleukin 1 (IL-1), tumor necrosis factor .alpha., and interleukin 6, are often produced in response to tissue injury and contribute to several host responses such as weight loss, anorexia, and acute-phase protein synthesis. However, the role of IL-1 in specific tissue responses is unclear. To test our hypothesis that specific in vivo blockade of IL-1''s action might inhibit the catabolic host changes associated with inflammation, mice were passively immunized with a monoclonal antibody directed against the murine IL-1 receptor prior to initiation of a turpentine-induced sterile abscess. This antibody prevents IL-1-mediated proliferation of murine thymocytes in vitro by inhibiting IL-1.alpha. and IL-1.beta. by way of competition for a common receptor. Weight loss following turpentine challenge was prevented by daily injections of anti-IL-1 receptor monoclonal IgG. Body composition analysis confirmed that lean tissue and fat were preserved by passive immunization. Furthermore, pretreatment with an anti-IL-1 receptor monoclonal antibody significantly attenuated the plasma amyloid P and interleukin 6 responses but did not affect the decline in plasma albumin or the increase in circulating corticosterone. Passive immunization of similar mice with polyclonal antisera against another cytokine, tumor necrosis factor .alpha., failed to prevent either the weight loss or hepatic acute-phase protein changes observed in this inflammatory model. These findings suggest that IL-1 orchestrates weight loss and body compositional changes during inflammation and contributes to the induction of interleukin 6 and acute-phase protein synthesis.