Dexamethasone given prior to cardiopulmonary bypass (CPB) blunts post-operative inflammatory response, which is evidenced by reduced serum levels of pro-inflammatory cytokines.[1] We hypothesized, that genetic variants may modify the effect of dexamethasone upon inflammatory response. In a post-hoc analysis of 511 adult patients from the INFLACOR-trial, post-operative serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF), intracellular adhesion molecule-1 (ICAM-1), serum E-selectin (ESEL), and C-reactive protein (CRP) were tested for association with single nucleotide variants (SNV) of relevant genes and with one dose of dexamethasone (median - 0.6 mg/kg) given before CPB. Genotypic and allelic associations were evaluated in by dexamethasone use stratified analysis by Kruskal-Wallis (KW) test. Bonferroni correction was applied and is reported (BC). Of the 511 analyzed patients, 184 (36%) received dexamethasone resulting in decreased postoperative serum levels of ICAM-1 by 8.6% (p=0.029), serum E-selectin by 31% (p<10-4), TNFα by 41% (p=0.002), CRP by 44% (p<10-4), and IL-6 by 83% (p<10-4). All analyzed SNVs were in Hardy-Weinberg equilibrium. Postoperative IL-6 levels did not differ between the IL6 rs1800796 genotypes in placebo-treated patients (p=0.221). In patients receiving dexamethasone IL-6 serum levels were associated with rs1800796 genotypes (p=0.017), (Fig. 1A) independent of dexamethasone dose and CPB duration. The C allele of rs1800796 was associated with a reduced effect of dexamethasone upon IL-6 levels (BC p=0.0038) compared to the G allele. Postoperative CRP levels were lower in the heterozygous genotype of CRP rs1800947 (p=0.0001) in patients not receiving dexamethasone.(Fig.1B) Dexamethasone decreased postoperative CRP levels (p=0.0000), but the CRP level difference between the two genotypes was similar in patients receiving (ca. 19%, BC p=0.039) and not receiving dexamethasone (ca. 22%, BC p=0.0004), so the effect of dexamethasone was not genotype dependant. The analyzed variants of E-Sel rs1805193 (G>T), ICAM1 rs5498 (A>G) and TNF rs1800629 (G>A) genes tested negative for associations with postoperative levels of E-selectin, ICAM-1 and TNFα respectively, regardless of dexamethasone use. Dexamethasone given in one dose before CPB reduces postoperative cytokine and CRP levels, and seems to have genotype-dependant effect on IL-6 gene expression. If these results could be replicated, and the associations would be related to outcome - i.e.: postoperative acute kidney injury or atrial fibrillation - they could pose rationale for a ‘patient-suited’, genotype-adjusted dexamethasone prophylaxis in patients undergoing cardiac surgery on CPB. 1. Engelman RM, et al. Influence of steroids on complement and cytokine generation after cardiopulmonary bypass. Ann Thor Surg 1995; 60:801-804.