Bilfinger T V, Hughes T K, Rodriguez M, Glass R, Casares F, Stefano G B
Department of Surgery, University of New York at Stony Brook 11794-8191, USA.
Int J Cardiol. 1996 Apr 26;53 Suppl:S47-53. doi: 10.1016/0167-5273(96)02571-5.
Cardiopulmonary bypass (CPB) results in a diffuse inflammatory response characterized in part by hyperstimulation of leukocytes. We have previously shown that this hyperstimulation appears to be due, in part, to an increase in the release of biological response modifiers (BRMs) such as cytokines. In the present study, we evaluated the ability of a naturally occurring immunocyte inhibitory substance, alpha-melanocyte-stimulating hormone (alpha-MSH), to prevent the hyperstimulation caused by CPB. Monocytes and granulocytes were pretreated with alpha-MSH (10(-6) M) before exposing the cells to plasma obtained from patients who had undergone CPB, as CPB plasma would stimulate native monocytes and granulocytes in a manner similar to that observed in CPB patients. Pretreatment of these cells with alpha-MSH significantly diminished the hyperstimulation induced by CPB plasma in a concentration-dependent manner. In contrast, when the cells were first or simultaneously exposed to CPB plasma and then to alpha-MSH, alpha-MSH had no effect. Furthermore, use of the specific neutral endopeptidase inhibitor, phosphoramidon, significantly increased the efficacy of alpha-MSH in inhibiting CPB-induced immunocyte activation. The data demonstrate that pretreatment of monocyte/macrophages and granulocytes with alpha-MSH effectively inhibits the immune hyperstimulation induced by CPB-plasma exposure. In addition, the data strongly suggest that preexposure to other naturally occurring immune inhibitory substances may diminish the hyperstimulation associated with CPB. The study also further confirms that this hyperstimulation may, in part, be due to BRMs released from immunocytes.
体外循环（CPB）会引发一种弥漫性炎症反应，其部分特征为白细胞的过度刺激。我们之前已经表明，这种过度刺激似乎部分归因于生物反应调节剂（BRM）如细胞因子释放的增加。在本研究中，我们评估了一种天然存在的免疫细胞抑制物质α-黑素细胞刺激素（α-MSH）预防CPB引起的过度刺激的能力。在将细胞暴露于接受CPB治疗患者的血浆之前，先用α-MSH（10⁻⁶ M）预处理单核细胞和粒细胞，因为CPB血浆会以与在CPB患者中观察到的方式类似的方式刺激天然单核细胞和粒细胞。用α-MSH预处理这些细胞以浓度依赖的方式显著减轻了CPB血浆诱导的过度刺激。相比之下，当细胞先或同时暴露于CPB血浆然后再暴露于α-MSH时，α-MSH没有效果。此外，使用特异性中性内肽酶抑制剂磷酰胺素可显著提高α-MSH抑制CPB诱导的免疫细胞激活的功效。数据表明，用α-MSH预处理单核细胞/巨噬细胞和粒细胞可有效抑制CPB血浆暴露诱导的免疫过度刺激。此外，数据强烈表明，预先暴露于其他天然存在的免疫抑制物质可能会减轻与CPB相关的过度刺激。该研究还进一步证实，这种过度刺激可能部分归因于免疫细胞释放的BRM。
