Regulated upon activation, normal T-cell expressed and secreted chemokine and interleukin-6 in rheumatic pulmonary hypertension, targets for therapeutic decisions

Background: Recent studies have highlighted the possible influence of chemokines and cytokines on several types of pulmonary arterial hypertension (PAH). Increasing interest has also been focussed on their role as a cause of post-cardiopulmonary bypass (CPB) organ dysfunction. Hypothesis: Chemokines and cytokines are involved in the pathobiology of rheumatic PAH. Methods: Serum levels of the chemokine, regulated upon activation, normal T-cell expressed and secreted (RANTES) and the cytokine interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) in 35 patients with rheumatic mitral valve disease and 10 matched healthy subjects (control group). Eleven patients (31.4%) had severe pulmonary hypertension. Subsequently, 23 patients underwent mitral valve replacement. The relation of RANTES and IL-6 circulating level with postoperative organ dysfunction was analysed through multiple organ dysfunction score (MODS). Results: Patients with severe PAH have a significantly higher mean serum level of RANTES compared with other patients (6138.6 ± 3543.8 pg/ml vs 1818.2 ± 475.2 pg/ml, p = 0.0003). The serum level of IL-6 in the patients was statistically different from that of the control (378 ± 50.8 pg/ml vs 262 ± 90.5 pg/ml, respectively, p = 0.002). Patients who required postoperative inotropes had higher preoperative and post-CPB levels of both RANTES and IL-6. While patients with postoperative lung dysfunction had higher levels of IL-6 preoperatively and post-CPB and lower levels of RANTES post-CPB. Conclusions: RANTES and IL-6 should be investigated as potential therapeutic targets in the control of rheumatic PAH. Improved understanding of the contribution of RANTES and IL-6 to adverse postoperative complications can lead to improved patient outcome.