Association of interferon-gamma and interleukin-4 gene polymorphisms with susceptibility to brucellosis in Iranian patients

Activation of macrophages and their antimicrobial activities by interferon-gamma (IFN-γ) plays a crucial role in controlling Brucella infection. Interleukin-4 (IL-4) antagonizes the macrophage activity effects of IFN-γ and thus inhibits cell-mediated immune reactions. Given that the production of IFN-γ and IL-4 are under genetic control, we investigated the relationship between these two cytokine gene polymorphisms and the susceptibility to brucellosis. Hundred and ninety-five patients with brucellosis and 91 healthy animal husbandmen who owned infected animals and consumed their contaminated dairy products were selected to participate in this study. All individuals were genotyped for IFN-γ and IL-4 gene polymorphisms at positions +874 and −590, respectively. Results showed that IFN-γAA genotype was significantly more prevalent (P = 0.03) and IL-4CC genotype was significantly less frequent (P = 0.034) in the patient group compared to the control group. Also, the frequency of IFN-γ/IL-4 combination of genotype (IFN-γTT/IL-4CC) and allele (IFN-γT/IL-4C) were significantly higher in the controls than in the patients (P = 0.033 and P = 0.0035, respectively). Data suggest that individuals who have IFN-γAA genotype are more susceptible, and those who carry IL-4CC genotype are more resistant to brucellosis. We also suggest that individuals who carry IFN-γT/IL-4C or IFN-γTT/IL-4CC can be more resistant to Brucella infection.