Analysis of IL-10, IL-4 and TNF-α polymorphisms in drug-induced liver injury (DILI) and its outcome

Background/Aims The aim of this study was to assess whether genetic polymorphism of three important candidate cytokine genes, IL-10 (−1082G/A, −819C/T, and −592C/A), IL-4 (−590C/T) and TNF-α (−308G/A), play a role in the susceptibility to developing drug-induced liver injury (DILI), and in determining its phenotypic expression and severity. Methods Cytokine genotyping was analysed using TaqMan 5′ allelic discrimination assay in 140 DILI patients (mean age 51 y, range 13–82, with equal sex distribution) included in the Spanish Registry and 268 healthy controls. Results Genotypes, haplotypes and allele frequencies were similar for both cases and controls. The low IL-10 producing haplotype was more prevalent in DILI patients with the absence of peripheral blood eosinophilia (Pc = 0.004, OR = 5.29, 95% CI: 2.04–13.67), revealing significantly lower median eosinophil counts (0.19 × 109 L; P < 0.0002) compared to the intermediate (0.24 × 109 L) and high (0.40 × 109 L) IL-10 haplotypes. All cases with serious DILI outcome carried low or intermediate IL-10 producing haplotype and had normal or low eosinophil counts. Conclusions IL-10, IL-4 and TNF-α genetic polymorphisms were not related to the risk of developing DILI. Low IL-10 producing haplotype is associated with low eosinophil count, absence of eosinophilia and may be associated with worse clinical outcome from DILI.