Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations

To evaluate cytokine balance related to cardiopulmonary bypass, we prospectively investigated 11 infants undergoing cardiac operations for congenital heart disease. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-8) and the antiinflammatory cytokine interleukin-10 were measured at multiple time points before, during, and after bypass. Tumor necrosis factor-alpha and interleukin-8 values were within normal range before the operation. These values increased significantly during bypass, reaching their peaks after protamine administration (tumor necrosis factor-alpha, 133.6 +/- 124.9 pg/ml; mean +/- standard deviation; p<0.005) and 2 hours after termination of the procedure (interleukin-8, 92.1 +/- 44.1 pg/ml; p < 0.01). Tumor necrosis factor-alpha and interleukin-8 equaled normal prebypass values from the first postoperative day on. Interleukin-10 levels were within normal range before the operation and were already significantly increased 10 minutes after initiation of bypass (interleukin 10, 39.4 +/- 34.3 pg/ml; p<0.05). These levels remained elevated throughout the procedure but returned to normal after protamine administration. A second significant release of interleukin-10 occurred from the early postoperative period on, reaching its peak 24 hours after termination of cardiopulmonary bypass (interleukin-10, 351.6 +/- 304.0 pg/ml; p < 0.01). Interleukin-10 values were normal on the second postoperative day in all patients. Interleukin-10 kinetics showed an inverse pattern compared with tumor necrosis factor-alpha and interleukin-8. This difference suggests an interplay between proinflammatory and antiinflammatory cytokines released during and after cardiopulmonary bypass. Interleukin-10 levels measured 4 and 24 hours after bypass strongly correlated with the degree of hypothermia during bypass (Spearman's correlation coefficient, -0.77 [p < 0.01] and -0.89 [p < 0.0005], respectively); these levels did not correlate with duration of bypass and aortic crossclamping, however. This result suggests that besides immunologically mediated production of interleukin-10, hypothermia itself could modulate interleukin-10 production. In conclusion, this study demonstrates interleukin-10 production, in addition to interleukin-8 and tumor necrosis factor-alpha synthesis, in response to cardiopulmonary bypass in infants. Interleukin-10 could play a protective role by down-regulating proinflammatory cytokine release during and after cardiopulmonary bypass.