Tumor necrosis factor-α production in whole blood after cardiopulmonary bypass: Downregulation caused by circulating cytokine-inhibitory activities

Objectives: Cardiopulmonary bypass is associated with the release of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, interleukin 6, and interleukin 8) and anti-inflammatory cytokines (interleukin 10 and transforming growth factor β1). On the one hand this cytokine release is related to the postoperative systemic inflammatory response syndrome, and on the other hand it is related to deterioration of the immune system, for example in monocyte or polymorphonuclear neutrophil function, leading to an increased susceptibility to infections. To gain further insight into the alterations of immune cell reactivity and possible regulatory mechanisms, we studied lipopolysaccharide-induced tumor necrosis factor α synthesis in whole blood from cardiac surgical patients. Methods: Fifteen patients undergoing elective heart surgery with cardiopulmonary bypass were included in the study. Ex vivo lipopolysaccharide-induced tumor necrosis factor α synthesis was measured in a whole blood assay before, during, and after bypass. Corresponding tumor necrosis factor α messenger RNA levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction. In addition, the influence of patient serum on whole blood responsiveness and its relationship to anti-inflammatory cytokines were evaluated in vitro. Results: Tumor necrosis factor α synthesis was significantly reduced after 30 minutes of cardiopulmonary bypass and showed the lowest values at the end of bypass (mean ± SD 0.109 ± 0.105 ng/106 white blood cells after 30 minutes of bypass and 0.050 ± 0.065 ng/106 white blood cells at the end of bypass, vs 0.450 ± 0.159 ng/106 white blood cells preoperatively, P