Polymorphisms of cytokine genes and their correlations with efficiency of continuous treatment in patients with pulmonary tuberculosis

Current research in the field of an immunogenetics of tuberculosis is considered a key direction, since the treatment efficiency and outcomes of the disease in most cases depend on immunological and genetic features of the patient. Special attention should be paid to IL-10 value in development of protective immunity against tuberculosis. There are some contradictory data on influence of IL-10 on development of immune response in the patients with pulmonary tuberculosis which are published in several works. For example, L.G. Tarasova and colleagues connect the increased concentration of IL-10 with extensive destructive processes in pulmonary tissue, whereas while D. Higgins and coauthors show its key role in protection against chronic pneumonia. The objective of our study was to evaluate relations between several cytokine gene polymorphisms (IL1β, IL4, IL10, TNF), and their expression levels of in the course of continuous chemotherapy. Whole venous blood was taken for the molecular and genetic analysis was perfoemed, with subsequent isolation of genomic DNA and carrying out real-time PCR for genotyping of SNPs. Concentration of cytokines in blood serum were defined by method of enzyme immunoassay. Statistical analysis included check of normality of distribution of data, nonparametric correlations and comparison of qualitative characters. The assessment of compliance of genotypes to distribution of Hardy–Weinberg was carried out with use of criterion χ2 Pearson. To measure the cytokine concentrations (IL-1β, IL-4, IL-6, TNFα, IFNγ, IL-10) in blood serum, we used peripheral venous blood taken in fasting state at a 5-mL volume. Enzyme immunoassay was made with reagent sets from JSC Vektor Best-Tsitokiny according to the instructions from manufacturer. In the course of specific chemotherapy at the continuation phase, a more adverse course of a disease was registered among the patients with a pulmonary tuberculosis harboring IL4-589CC genotype, when compared with those who have IL4-589CT+TT genotype. In the persons with IL10-592CA+AA genotype, a less favorable course of the disease was observed at the intensive phase of therapy, in comparison with patients who had IL10-592CC genotype. Thus, process of interaction between microorganisms and macroorganisms in case of a tuberculosis infection represents a quite complicated process involving a set of immune response elements. Interactions within this system are controlled by means of cytokines, the mediators of cellular interactions.