Gullestad L, Aass H, Fjeld J G, Wikeby L, Andreassen A K, Ihlen H, Simonsen S, Kjekshus J, Nitter-Hauge S, Ueland T, Lien E, Frøland S S, Aukrust P
Department of Cardiology, Medical Department, Rikshospitalet, Oslo, Norway.
Circulation. 2001 Jan 16;103(2):220-5. doi: 10.1161/01.cir.103.2.220.
Congestive heart failure (CHF) is characterized by enhanced immune activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immunoglobulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF).
Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated cardiomyopathy), were randomized in a double-blind fashion to receive therapy with IVIG or placebo for a total period of 26 weeks. Our main findings were that (1) IVIG, but not placebo, induced a marked rise in plasma levels of the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antagonist, and soluble tumor necrosis factor receptors; (2) significantly correlated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26+/-2% to 31+/-3% (P:<0.01), and this was found independent of the cause of heart failure; and (3) N-terminal pro-atrial natriuretic peptide decreased significantly after induction therapy and continued to decrease toward the end of study during IVIG therapy (P:<0.001) but remained unchanged during placebo.
We demonstrated an IVIG-induced change in the balance between inflammatory and anti-inflammatory cytokines that favored an anti-inflammatory net effect in CHF. This effect was significantly correlated with an improvement in LVEF, suggesting a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in CHF patients.
充血性心力衰竭（CHF）的特征是免疫激活增强，免疫介导机制可能在该疾病中起致病作用。基于静脉注射免疫球蛋白（IVIG）的免疫调节作用，我们推测IVIG可下调CHF患者的炎症反应，并对左心室射血分数（LVEF）产生潜在的有益影响。
40例慢性症状性CHF且LVEF<40%的患者，根据病因（即缺血性和特发性扩张型心肌病）分层，以双盲方式随机接受IVIG或安慰剂治疗，为期26周。我们的主要发现是：（1）IVIG而非安慰剂可使抗炎介质白细胞介素（IL）-10、IL-1受体拮抗剂和可溶性肿瘤坏死因子受体的血浆水平显著升高；（2）与这些抗炎作用显著相关的是，IVIG而非安慰剂可使LVEF从26±2%显著增加至31±3%（P<0.01），且这一结果与心力衰竭的病因无关；（3）诱导治疗后N末端前心钠素显著降低，在IVIG治疗期间至研究结束时持续降低（P<0.001），而在安慰剂治疗期间保持不变。
我们证明了IVIG可诱导CHF患者炎症和抗炎细胞因子之间的平衡发生变化，有利于产生抗炎净效应。这种效应与LVEF的改善显著相关，提示在CHF患者的最佳传统心血管治疗方案之外，免疫调节治疗具有潜在应用价值。
