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

J Hepatol. 2008 Jul;49(1):107-14. doi: 10.1016/j.jhep.2008.03.017. Epub 2008 Apr 22.


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-alpha (-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 x 10(9)L; P<0.0002) compared to the intermediate (0.24 x 10(9)L) and high (0.40 x 10(9)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-alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemical and Drug Induced Liver Injury* / epidemiology
  • Chemical and Drug Induced Liver Injury* / genetics
  • Chemical and Drug Induced Liver Injury* / immunology
  • Cytokines / genetics*
  • Eosinophils / cytology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / epidemiology
  • Haplotypes
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-4 / genetics
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Prevalence
  • Promoter Regions, Genetic / genetics
  • Registries
  • Risk Factors
  • Severity of Illness Index*
  • Spain / epidemiology
  • Tumor Necrosis Factor-alpha / genetics


  • Cytokines
  • IL4 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4