Elsevier

Human Immunology

Volume 64, Issue 7, July 2003, Pages 674-680
Human Immunology

Original contribution
IL-10 and TNF-α polymorphisms and the recovery from HCV infection

https://doi.org/10.1016/S0198-8859(03)00080-6Get rights and content

Abstract

Hepatitis C virus (HCV) infection becomes chronic in about 85% of infected individuals, whereas only 15% of infected people clear spontaneously the virus. It is conceivable that the host immunogenetic background influences the course of infection in term of recovery. Thus, in this study we have evaluated the effect of functionally relevant polymorphisms at tumor necrosis factor-α (TNFα, i.e., 2 biallelic polymorphisms at nt -863 and nt-308 of the promoter) and interleukin-10 (IL-10) loci (i.e., 1 biallelic polymorphism at nt -1082 of the promoter), on the clearance of HCV infection. To this purpose, we compared 18 Sicilian patients who had spontaneously recovered from previous HCV infection with 42 Sicilian patients with current HCV infection and 135 Sicilian healthy patients. The results demonstrate a decreased frequency of the -863CC TNF-α promoter genotype (involved in high production of this pro-inflammatory cytokine) and an increased frequency of the -1082GG IL-10 promoter genotype (involved in high production of this anti-inflammatory cytokine) in patients recovered from HCV infection. The evaluation of combined TNF-α and IL-10 genotypes revealed a significant increase of the “anti-inflammatory genotype” (low-TNF/high-IL-10 producers) in resolved HCV infection group compared with patients with persistent HCV infection. On the whole, our findings suggest that a genetically determined control of the HCV-induced inflammatory response may play a role in the resolution of HCV infection.

Section snippets

Abbreviations

    EIA

    enzyme immunoassay

    HCV

    hepatitis C virus

    HLA

    human leukocyte antigens

    IFN

    interferon

    IL

    interleukin

    RIBA

    reverse immunoblotting assay

    SNP

    single nucleotide polymorphism

    TNF

    tumor necrosis factor

Patients

Eighteen Sicilian blood donors (age, 45.0 ± 1.3; 12 men and 6 women) with anti-HCV positivity without chronic infection gave informed consent and entered the study. These patients had spontaneously recovered from previous HCV infection as demonstrated by anti-HCV positive with persistently normal aminotransferases and negative HCV-RNA on three different tests 4 months apart. Data from this group were compared with those from 42 Sicilian patients (age, 45.3 ±3.2 years; 20 men and 22 women) with

Results

The clean effect of a given gene is a function of the gene pair combination received from parents and for both TNF-α and IL-10 SNPs a gene dosage effect on cytokine production has been claimed 8, 28. Thus, we have evaluated the frequencies of the different genotypes in the subjects with spontaneous recovery from HCV infection, in patients with chronic HCV infection and in healthy patients.

As reported in Table 1, a significant different distribution (p = 0.002) of -863C→A TNF-α genotypes was

Discussion

This study demonstrates that TNF-α gene SNP -863C→A and IL-10 gene SNP -1082G→A were significantly associated to a spontaneous clearance of HCV in Sicilians. TNF-α and IL-10 have predominantly opposing roles in the inflammatory responses. TNF-α has a wide range of proinflammatory activities, determining strength, effectiveness, and duration of local and systemic inflammatory reactions [30]. The type 2 cytokine IL-10, besides promoting humoral immune responses, limits and terminates inflammatory

Acknowledgements

These studies have been supported by grants from Ministry of Education, University and Research, Rome, ex 60% to D.L., G.C.R., G.C., and C.C.

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