The ex vivo production of tumor necrosis factor-α (TNF-α) in men: relationship to cytokine balance during cardiopulmonary bypass

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Objectives

To discriminate patients with strong or weak ex vivo TNF-α synthesis in response to whole blood stimulation with endotoxin (LPS) and to relate this ex vivo response to cytokine balance during and after cardiac surgery with cardiopulmonary bypass (CPB).

Patients and methods

19 patients scheduled for coronary artery bypass graft (CABG) with CPB and 29 adult volunteers were entered into the study. Whole blood was stimulated with LPS, incubated for 16 h and TNF-α concentrations determined in the culture supernatant. Results obtained in both patients and volunteers were pooled. Individuals showing TNF-α concentrations lower or higher than the median value of 1052 pg/ml were defined as low and high responders, respectively. In the 19 patients, cytokine balance during and after CPB was evaluated by the plasma concentrations of TNF-α, interleukin (IL)-8 and IL-10.

Results

In patients undergoing cardiac surgery, perioperative cytokine plasma levels were not significantly different in both low and high responders. In these two groups ex vivo TNF-α production did not correlate with either TNF-α or IL-8 plasma levels measured during and after CPB. In contrast, ex vivo TNF-α production inversely correlated with IL-10 plasma concentrations observed four hours after the end of CPB in the low responder group (Spearman, -0.76, P=0.01) and tended to do so in the high responder group (Spearman, -0.62, P=0.1).

Conclusion

In our series, the ex vivo production of TNF-α does not allow us to predict the magnitude of the systemic inflammatory response related to cardiac surgery, as evaluated by the plasma levels of TNF-α and IL8 during and after CPB. The negative correlation observed between the ex vivo TNF-α production and the production of IL-10 after CPB suggests that patients with a low ex vivo capability to synthesize the pro-inflammatory TNF-α have a high potential to synthesize the anti-inflammatory cytokine IL-10 in vivo. Whether this profile can be considered a risk factor for morbidity after cardiac surgery, as it has been shown for infectious diseases remains to be assessed.