Cytokine gene polymorphism in the regulation of inflammation and immunity

During last years a lot of data have been accumulated concerning the role of single nucleotide polymorphisms (SNP), forming specific alleles of certain genes, in the individual variations of immune reactivity. Genetic functional polymorphisms of the early inflammatory genes, especially that of cytokine genes are responsible for the mode of defense reactions and predisposition to some illness. The aim of this study was to investigate the associations of IL-1 beta gene (IL1B) and IL-1 receptor antagonist gene (IL1RA) polymorphism and compare it to the cytokine production levels in healthy donors and in patients with chronic rhinosinusitis. Genomic DNA was extracted from the peripheral blood of 53 patients and 54 healthy volunteers, IL-1beta and IL-1Ra gene polymorphism was analyzed by polymerase chain reaction (PCR) amplification оf the polymorphic site, followed by site-specific restriction digestion. Two sites were examined: IL-1B (+3953 C>T, intron 5). IL-1RA (86 bp variable tandem repeat, intron 2). IL-1B. IL-1RA and IL-8 levels in supernatants of LPS-stimulated peripheral blood leukocytes were measured using cytokine-specific ELISA. The results showed that there were significant differences in the frequencies of alleles or genotypes of IL-1В and IL-1RA between patients with chronic rhinosinusitis and controls. Combination of normal 1/1 variants of IL-1B and IL-1RA genes was 10 times higher in donors compared to patients with chronic rhinosinusitis (20,2% versus 2,1%. respectively) and combination of IL-1B 1/2 with IL-1RA 2/2 genotypes was nearly 15 times higher in patients (30,1%) than in donors (2,1%). Different combinations of cytokine alleles correlated with the clinical manifestations of rhinosinusitis. Our findings suggest that the IL-1 family gene cluster polymorphism may play a significant role in the pathogenesis of chronic rhinosinusitis probably due to the disregulation in the IL-1 family cytokines production. Nowadays SNP studies are very actual because it can make prognosis for the risk of severe illness development, and from the other hand in advance propose specific individual therapy, including modern immunotherapy.