Genotype and interleukin-10 responses after cardiopulmonary bypass

Abstract

Background. The pro- and anti-inflammatory cytokine balance has been implicated in outcome from inflammatory conditions, and cardiopulmonary bypass is associated with a marked inflammatory response. Interleukin-10 (IL-10) is an anti-inflammatory cytokine and levels have been shown to be highest in those patients who develop sepsis after trauma or surgery. IL-10 levels vary between individuals and genotype may dictate the IL-10 response. We therefore investigated IL-10 genotype, circulating IL-10 concentrations and outcome in terms of organ dysfunction 24 h after cardiopulmonary bypass. Methods. Blood samples were obtained from 150 patients before, and 3, and 24 h after cardiopulmonary bypass. IL-10 was measured by enzyme immunoassay. The single nucleotide polymorphism at - 1082 base pairs was detected by restriction fragment length polymorphism analysis. Post-bypass organ system dysfunction was defined prospectively. Results. IL-10 concentrations were increased 3 h after bypass (P<0.0001) and were still increased at 24 h (P<0.0001). Homozygosity for the G allele was associated with lower median (range) maximal IL-10 levels at 3 h (44 (13-136) pg ml-1) compared with the A allele (118 (39-472) pg ml-1; P=4.042). Those patients who developed at least one organ dysfunction (n=33) had higher IL-10 levels 3 h after surgery (242 (18-694) pg ml-1) compared with those without organ dysfunction (77 (7-586) pg ml-1; P=0.001, n=117). Conclusions. The G allele of the -1082 base pair single nucleotide polymorphism in the IL-10 gene is associated with lower IL-10 release after cardiopulmonary bypass. High levels of IL-10 secretion are associated with organ dysfunction 24 h after surgery.