Missov E, Campbell A, Lebel B
Department of Cardiology, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire, Montpellier, France.
Jpn Circ J. 1997 Sep;61(9):749-54. doi: 10.1253/jcj.61.749.
Cytokines are proteins with pleiotropic biological effects, but the pathophysiologic role of cytokine inhibitors in advanced cardiac disease remains unclear. We assessed the levels of tumor necrosis factor (TNF)-alpha and its soluble receptors I (sTNF-RI) and II (sTNF-RII), soluble interleukin-1 receptor antagonist (sIL-1 Ra), and interleukin-6 soluble receptor (IL-6 sR) in sera from 11 patients with severe chronic congestive heart failure (mean left ventricular ejection fraction 19 +/- 6%; mean symptom-limited oxygen consumption 13 +/- 4 ml/min per kg) and 11 healthy volunteers. The serum concentrations of TNF, sTNF-RI, and sIL-1 Ra, but not of sTNF-RII and IL-6 sR, were significantly increased in heart failure patients. Importantly, their symptom-limited oxygen consumption was strongly associated with both sTNF-RI (R = -0.68, p = 0.04) and sIL-1 Ra (R = -0.77, p = 0.01). These results suggest that cytokine inhibitors from different receptor families may be involved in functional disability, a characteristic feature in patients with severe congestive heart failure. Understanding the response of cytokine inhibitors to heart failure might have therapeutic value as interventions against cytokines become available.
细胞因子是具有多效生物效应的蛋白质，但细胞因子抑制剂在晚期心脏病中的病理生理作用仍不清楚。我们评估了11例严重慢性充血性心力衰竭患者（平均左心室射血分数19±6%；平均症状限制耗氧量13±4 ml/min per kg）和11名健康志愿者血清中肿瘤坏死因子（TNF）-α及其可溶性受体I（sTNF-RI）和II（sTNF-RII）、可溶性白细胞介素-1受体拮抗剂（sIL-1 Ra）以及白细胞介素-6可溶性受体（IL-6 sR）的水平。心力衰竭患者血清中TNF、sTNF-RI和sIL-1 Ra的浓度显著升高，而sTNF-RII和IL-6 sR的浓度未升高。重要的是，他们的症状限制耗氧量与sTNF-RI（R = -0.68，p = 0.04）和sIL-1 Ra（R = -0.77，p = 0.01）均密切相关。这些结果表明，来自不同受体家族的细胞因子抑制剂可能参与了功能障碍，这是严重充血性心力衰竭患者的一个特征。随着针对细胞因子的干预措施的出现，了解细胞因子抑制剂对心力衰竭的反应可能具有治疗价值。
