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.