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

Pachkoria, Ketevan; Lucena, M. Isabel; Crespo, Esperanza; Ruiz‐Cabello, Francisco; Lopez-Ortega, S.; Fernández, M.; Romero–Gómez, Manuel; Madrazo, A.; Durán, José Antonio; Dios, A. Malcón de; Borraz, Y.; Navarro, José María; Andrade, Raúl J.

doi:10.1016/j.jhep.2008.03.017

Cited by 72 publications

(57 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The minor alleles at positions -819 and -592 are the C allele in Asian populations [18-20,25,30], which is different to those seen in Western populations, being T and A alleles, respectively [22-24,26,31]. Although the minor allele at position -1082 is G in both Asian and Western populations, its frequency is quite different, over 40% in Western populations [21,22,26,31,32] and about 10% in Asian populations [19-21]. This leads to quite a difference in the common haplotypes between Asian and Western populations.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of the interleukin 10 promoter polymorphisms in Chinese Han patients with major trauma: genetic association studies

Chen

Jiang

et al. 2009

Critical Care

View full text Add to dashboard Cite

IntroductionAn excessive inflammatory response is thought to account for the pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS) after severe trauma. The interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS.MethodsA total of 308 patients with major trauma were included in this study. The genotypes of polymorphisms -1082, -819 and -592 were determined by polymerase chain reaction-restriction fragment length polymorphism. The IL-10 levels in the supernatants were determined with enzyme-linked immunoabsorbent assay.ResultsThe -1082A and -592A alleles were significantly associated with lower lipopolysaccharide-induced IL-10 production in an allele-dose dependent fashion. There was no significant difference for the -819 polymorphism. Except for the -1082 polymorphism, the -819 and -592 polymorphisms were not significantly associated with sepsis morbidity rate and MOD scores.ConclusionsOur results further confirm the functionality of the IL-10 promoter single nucleotide polymorphisms in relation to IL-10 production. They also suggest that individual difference in IL-10 production in trauma patients might be at least in part related to genetic variations in the IL-10 promoter region.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical relevance of the interleukin 10 promoter polymorphisms in Chinese Han patients with major trauma: genetic association studies

Chen

Jiang

et al. 2009

Critical Care

View full text Add to dashboard Cite

show abstract

“…The investigators speculated that polymorphisms that increase IL-10 or reduce IL-4 expression might contribute to a T-helper cell 2–mediated antibody response to diclofenac-induced neoantigens. Pachkoria et al 156 investigated IL-10, IL-4, and tumor necrosis factor-α genetic polymorphism in 140 patients with DILI from different agents and 268 healthy controls. IL-10 haplotypes that reduced expression levels were more common in patients with DILI without peripheral eosinophilia (OR, 5.29).…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

“…All DILI cases with serious outcomes carried haplotypes that resulted in low or intermediate levels of IL-10 expression, and had normal or low numbers of eosinophils. 156 The investigators attempted to correlate IL-10 genotypes with the severity of liver injury, but the study included too few cases of severe liver injury for this analysis.…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

Risk Factors for Idiosyncratic Drug-Induced Liver Injury

2010

View full text Add to dashboard Cite

Idiosyncratic drug-induced liver injury (DILI) is a rare disorder that is not related directly to dosage and little is known about individuals who are at increased risk. There are no suitable preclinical models for the study of idiosyncratic DILI and its pathogenesis is poorly understood. It is likely to arise from complex interactions among genetic, nongenetic host susceptibility, and environmental factors. Nongenetic risk factors include age, sex, and other diseases (eg, chronic liver disease or human immunodeficiency virus infection). Compound-specific risk factors include daily dose, metabolism characteristics, and propensity for drug interactions. Alcohol consumption has been proposed as a risk factor for DILI from medications, but there is insufficient evidence to support this. Many studies have explored genetic defects that might be involved in pathogenesis and focused on genes involved in drug metabolism and the immune response. Multicenter databases of patients with DILI (the United States Drug Induced Liver Injury Network, DILIGEN, and the Spanish DILI registry) are important tools for clinical and genetic research. A genome-wide association study of flucloxacillin hepatotoxicity has yielded groundbreaking results and many similar studies are underway. Nonetheless, DILI is challenging to investigate because of its rarity, the lack of experimental models, the number of medications that might cause it, and challenges to diagnosis.

show abstract

“…Indeed, several cytokines [12-16], and individual or small groups of cytokines have been reported to be altered in a few experimental studies of DILI [17-21]. For example, in one study in humans, genetic polymorphisms associated with lower production of IL-10, were associated with lower eosinophil counts and poorer outcomes [13]. …”

Section: Introductionmentioning

confidence: 99%

Profiles of Serum Cytokines in Acute Drug-Induced Liver Injury and Their Prognostic Significance

et al. 2013

View full text Add to dashboard Cite

Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United-States. The aim of the study was to describe serum immune profiles associated with acute DILI, to investigate whether there are profiles associated with clinical features or types of DILI and/or with prognosis, and to assess temporal changes in levels. Twenty-seven immune analytes were measured in the sera of 78 DILI subjects in the Drug-Induced Liver Injury Network (DILIN) and compared with 40 healthy controls. Immune analytes (14 cytokines, 7 chemokines and 6 growth factors) were measured by BioPlex multiplex ELISA at DILI onset and after 6 months. A modeling process utilizing immune principles was used to select a final set of variables among 27 immune analytes and several additional clinical lab values for prediction of early death (within 6 months of DILI onset). Nineteen of the 27 immune analytes were differentially expressed among healthy control, DILI onset and 6-month cohorts. Disparate patterns of immune responses, especially innate and adaptive cellular (mostly TH17) immunity were evident. Low values of four immune analytes (IL-9, IL-17, PDGF-bb and RANTES) and serum albumin are predictive of early death [PPV = 88% (95% CI, 65%-100%), NPV = 97% (95% CI, 93%-100%), accuracy = 96% (95% CI, 92%-100%)]. ConclusionsAcute DILI is associated with robust and varying immune responses. High levels of expression of cytokines associated with innate immunity are associated with a poor prognosis, whereas high levels of expression of adaptive cytokines are associated with good long-term prognosis and eventual recovery. Serum immune analyte profiles at DILI onset appear to be of prognostic, and perhaps, diagnostic significance.

show abstract

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

Cited by 72 publications

References 42 publications

Clinical relevance of the interleukin 10 promoter polymorphisms in Chinese Han patients with major trauma: genetic association studies

Clinical relevance of the interleukin 10 promoter polymorphisms in Chinese Han patients with major trauma: genetic association studies

Risk Factors for Idiosyncratic Drug-Induced Liver Injury

Profiles of Serum Cytokines in Acute Drug-Induced Liver Injury and Their Prognostic Significance

Contact Info

Product

Resources

About