Pulmonary thromboendarterectomy (PTE) is an effective but challenging treatment for chronic thromboembolic pulmonary hypertension (CTEPH). PTE is associated with marked hemodynamic instability in the perioperative course, suggesting the involvement of circulating mediators. The aim of this study was to characterize the expression of proinflammatory and anti-inflammatory cytokines in patients undergoing PTE.Fourteen patients with CTEPH (mean [+/- SD] pulmonary vascular resistance, 1,056 +/- 399 dyne.s.cm(-5)) underwent PTE using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Peripheral arterial blood samples were drawn prior to patients undergoing sternotomy, during CPB, before and after DHCA, and 0, 8, 16, 24, and 48 h after surgery. An enzyme-linked-immunosorbent assay was used to analyze the plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Seven patients undergoing aortic arch replacement (ARCH) in DHCA served as a control group.Prior to and during PTE, the CTEPH patients exhibited elevated TNF-alpha levels, which decreased within the first 24 postoperative hours (p = 0.02). There was no TNF-alpha release among patients in the ARCH group. IL-6 levels were similar in both groups throughout the perioperative course. A profound anti-inflammatory response was observed in the PTE group, which was reflected by elevated IL-10 levels prior to surgery and a marked peak level immediately after surgery. A positive correlation was found between maximum vasopressor support and peak levels of IL-6 (r = 0.82) in the PTE patients.Heart failure due to CTEPH appears to generate a pronounced inflammatory response with the release of proinflammatory and anti-inflammatory cytokines. PTE results in the rapid normalization of preoperatively elevated TNF-alpha levels. IL-6-mediated systemic inflammatory cascades may be involved in the regulation of peripheral vascular tone after PTE.