Effects of preoperative statin therapy on cytokines after cardiac surgery

Introduction: In addition to their lipid-lowering action, it has been demonstrated that statins can exert direct anti-inflammatory effects. We investigated the effect of preoperative statin therapy on systemic inflammatory markers and myocardial NF-kappa B inhibitor I kappa B-alpha after cardiac surgery. Methods: Thirty-six patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass (CPB) with cardioplegia were divided into two groups (statin group, n = 18; control group, n = 18). Plasma concentrations of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF alpha], interleukin [IL]-6, IL-8) and anti-inflammatory IL-10 were measured before and 1, 4, 10, and 24 hours (h) after CPB. Phosphorylated I kappa B-alpha/total IKB-alpha ratio was assessed before and after CPB in right atrial biopsies. Results: Baseline and operative data did not differ between groups. Statin therapy was associated with lower preoperative low-density lipoprotein levels compared to control (73 +/- 6 vs. 92 +/- 6 mg/dL; p = 0.03). Release of IL-6 was attenuated in the statin group at 4 h (2270 +/- 599 vs. 5120 +/- 656 pg/ml; p<0.01) and 10 h (1295 +/- 445 vs. 3116 +/- 487 pg/ml; p<0.05) compared to the control group. IL-10 increased after surgery in both groups (p < 0.05), but was higher in the statin group at 1 h (66 +/- 15 vs. 26 +/- 16 pg/ mL; p < 0.01). Phosphorylated I kappa B-alpha/total I kappa B-alpha ratio before CPB did not differ between groups, but was elevated after CPB in both groups (p < 0.05), indicating enhanced degradation of I kappa B-alpha. Statin therapy had no effect on TNF alpha and IL-8. Conclusions: Preoperative statin therapy attenuates the release of pro-inflammatory IL-6 and up-regulates anti-inflammatory IL-10 after cardiac surgery with cardioplegia, but fails to inhibit phosphorylation of myocardial I kappa B-alpha.