University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.
Washington University in St Louis, St Louis, MO, United States of America.
Int J Cardiol. 2021 Sep 15;339:93-98. doi: 10.1016/j.ijcard.2021.06.022. Epub 2021 Jul 3.
Immune dysregulation is implicated in the development and clinical outcomes of peripartum cardiomyopathy (PPCM).
98 women with PPCM were enrolled and followed for 1 year postpartum (PP). LVEF was assessed at entry, 6-, and 12-months PP by echocardiography. Serum levels of soluble interleukin (IL)-2 receptor (sIL2R), IL-2, IL-4, IL-17, IL-22, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured by ELISA at entry. Cytokine levels were compared between women with PPCM by NYHA class. Outcomes including myocardial recovery and event-free survival were compared by cytokine tertiles. For cytokines found to impact survival outcomes, parameters indicative of disease severity including baseline LVEF, medications, and use of inotropic and mechanical support were analyzed. Levels of proinflammatory cytokines including IL-17, IL-22, and sIL2R, were elevated in higher NYHA classes at baseline. Subjects with higher IL-22 levels were more likely to require inotropic or mechanical support. Higher levels of TNF-α and IL-22 were associated with poorer event-free survival. Higher TNF-α levels were associated with lower mean LVEF at entry and 12 months. In contrast, higher levels of immune-regulatory cytokines such as IL-4 and IL-2 were associated with higher LVEF during follow up.
Proinflammatory cytokines IL-22 and TNF-α were associated with adverse event-free survival. IL-17 and IL-22 were associated with more severe disease. In contrast, higher levels of IL-2 and IL-4 corresponded with higher subsequent LVEF. Increased production of TH17 type cytokines in PPCM correlated with worse disease and outcomes, while an increased immune-regulatory response seems to be protective.
免疫失调与围产期心肌病（PPCM）的发生和临床结局有关。
共纳入 98 例 PPCM 女性患者，产后随访 1 年。超声心动图于入组时、产后 6 个月和 12 个月评估左心室射血分数（LVEF）。ELISA 法检测入组时血清可溶性白细胞介素（IL）-2 受体（sIL2R）、IL-2、IL-4、IL-17、IL-22、肿瘤坏死因子（TNF）-α 和干扰素（IFN）-γ 水平。根据 NYHA 分级比较 PPCM 患者的细胞因子水平。根据细胞因子三分位数比较心肌恢复和无事件生存的结局。对影响生存结局的细胞因子进行分析，包括基线 LVEF、药物、正性肌力和机械支持的使用等反映疾病严重程度的参数。较高 NYHA 分级的患者基线时促炎细胞因子如 IL-17、IL-22 和 sIL2R 水平升高。IL-22 水平较高的患者更可能需要正性肌力或机械支持。较高的 TNF-α 和 IL-22 水平与较差的无事件生存相关。较高的 TNF-α 水平与入组时和 12 个月时较低的平均 LVEF 相关。相比之下，较高水平的免疫调节细胞因子如 IL-4 和 IL-2 与随访期间更高的 LVEF 相关。
促炎细胞因子 IL-22 和 TNF-α 与不良的无事件生存相关。IL-17 和 IL-22 与更严重的疾病相关。相比之下，IL-2 和 IL-4 水平升高与随后的 LVEF 更高相关。PPCM 中 TH17 型细胞因子的产生增加与疾病和结局恶化相关，而免疫调节反应增加似乎具有保护作用。
