Elsevier

Cytokine

Volume 35, Issues 3–4, August 2006, Pages 143-147
Cytokine

Interleukin-10 (IL-10) gene polymorphism as a potential host susceptibility factor in tuberculosis

https://doi.org/10.1016/j.cyto.2006.07.015Get rights and content

Abstract

Several genes encoding for different cytokines may play crucial roles in host susceptibility to tuberculosis (TB), since the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphism. The association of the cytokine gene polymorphisms with the development of TB was investigated in this study. DNA samples were obtained from a Turkish population of 81 patients with the different clinical forms of TB, and 50 healthy control subjects. All genotyping (IL-6, IL-10, IFN-γ, TGF-β and TNF-α) experiments were performed using sequence-specific primers PCR (PCR-SSP). Analysis of allele frequencies showed that IL-10 −1082 G allele frequency was significantly more common in TB patients than healthy controls (37.7% vs 23.0%, p: 0.014). No statistically significant differences were observed between the different clinical forms of the disease. These results suggest that the polymorphisms in IL-10 gene may affect susceptibility to TB and increase risk of developing the disease. To confirm the biological significance of our results, further studies should be performed on other population groups.

Introduction

Tuberculosis (TB) remains to be a leading cause of morbidity and mortality in developing countries. However, the incidence of disease increases in developed countries [1]. One third of the world’s population is infected by Mycobacterium tuberculosis but only about 5% of the infected people develop disease within the first year of infection (primary TB) and other 5% develop the disease later in life (reactivation TB). At present it is impossible to predict in whom the disease will develop and progress through several stages from mild to severe. There are several reports demonstrating that host genetic factors play significant roles in susceptibility to TB [2]. Therefore, the identification of host genes responsible for susceptibility and resistance to TB should provide a significant contribution for understanding of the pathogenesis and may lead to the development of new prophylaxis and treatment strategies.

Cytokines produced at the site of disease after interactions between T lymphocytes and infected macrophages are essential for the pathogenesis of TB [3]. The course of M. tuberculosis infection is regulated by two distinct T cell cytokine patterns. T helper 1 (Th1) cytokines, IL-2 and IFN-γ, are associated with resistance to infection, whereas Th2 cytokines, IL-4 and IL-13, are associated with progressive disease [4]. In addition, IL-10, one of the T regulatory cytokines, seem to play a pivotal role during the chronic/latent stage of pulmonary TB, with increased production playing a potentially central role in promoting reactivation of TB [5]. Another T regulatory cytokine TGF-β, mainly produced by Th3 cells, may be beneficial or detrimental by inducing fibrosis or by contributing cavity formation, respectively, [6]. Of fundamental immunologic importance are the factors, that influence the nature of cytokine response, such as polymorphisms of cytokine genes. Polymorphisms in several cytokine genes have been described and demonstrated to influence gene transcription, leading to interindividual variations in cytokine production [7], [8]. Cytokine gene polymorphisms have been shown to be involved in the susceptibility, severity and clinical outcome of several diseases including infectious ones [7], [8], [9], [10].

The aim of this work was to determine whether there is any association between cytokine gene polymorphisms and susceptibility to TB. We performed a study in Turkish patients affected with different clinical forms of TB and healthy control subjects to determine the influence of single nucleotide polymorphisms in five cytokines (IL-6, IL-10, IFN-γ, TGF-β and TNF-α) on susceptibility and disease expression.

Section snippets

Patients and controls

Blood samples, collected in ethylenediamine tetraacetate sterile tubes, were obtained from 81 Turkish patients affected by different forms of TB (Table 1). TB was diagnosed on the basis of radiographic and clinical presentation, positive special staining and cultures for M. tuberculosis and, in some cases, the finding of caseating granulomas in biopsies. A control group was composed of 50 healthy organ donors, matched for age and sex, ethnicity and from the same geographical area as the

Results

We evaluated the frequencies of cytokine gene polymorphisms in patients affected by different clinical forms of TB (Table 1) and in healthy volunteers.

The frequency of IL-10 (−1082, −819, −592) GCC/ACC genotype was significantly higher in TB patients when compared with those of healthy controls (37.0% vs 20.0%, p: 0.04), whereas significantly lower frequencies of IL-10 ACC/ATA genotype was observed in the patient group (14.8% vs 32.0%, p: 0.02). Statistical significant differences for both

Discussion

Single nucleotide polymorphisms in several candidate genes have been linked to relatively increased risk for TB [9]. In this polymorphism-association study, we investigated the significance of the relationship between several cytokine gene polymorphisms and susceptibility to TB.

Interleukin-10 is a multifunctional cytokine first described as cytokine synthesis inhibitory factor, which inhibits IFN-γ cytokine production by Th1 cells in mice [11], [12]. It inhibits monocyte/macrophage function

Acknowledgment

This study was supported by the grant from Uludag University, Bursa, Turkey (Grant number 2002/35).

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