Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.

Туберкулез признан одной из самых серьезных медико-социальных проблем. Согласно последним статистическим данным, ежегодно количество больных туберкулезом увеличивается на 8-10 млн, около 3 млн из них умирают, причем 300 тыс.-дети [7]. Туберкулезная инфекция протекает достаточно длительное время и постепенно приводит к истощению пула участников иммунного ответа. Исследование цитокинового профиля имеет большое значение для оценки состояния иммунной системы при заболеваниях различного генеза, в том числе и туберкулезе. В настоящее время в лечебной практике применяется исследование содержания цитокинов в зависимости от клинических и морфологических проявлений активности гранулематозного воспаления [2, 5]. Важнейшим провоспалительным цитокином является интерферон-гамма (IFNγ), который продуцируется активированными Т-лимфоцитами и естественными киллерами (NK). IFNγ играет ведущую роль в генезе индуцированной туберкулезным антигеном в ткани легкого гранулемы посредством экспрессии адгезивных молекул и хемокинов, необходимых для рекрутирования моноцитов/макрофагов в очаг воспаления [1]. Известно, что уровень IFNγ в плазме крови

In this article, production of proinflammatory and anti inflammatory cytokines was investigated in vitro in tuberculin negative patients with infil trative, disseminated or fibrocavernous pulmonary tuberculosis. Along with basal hypersecretion of IFN γ, patterns of change in basal and BCG induced production of IL 2, IL 4, IL 10 and TGF β related to Th1 dependent and Th2 dependent immune responses have been described in sev eral clinical variants of tuberculosis. Negative tuberculin skin reaction due to Тh1 lymphocytes hypoergy was also caused by multidirectional changes in IL 4 and IL 10 production in infiltrative and disseminated pulmonary tuberculosis and by TGF β hypersecretion in patients with disseminated and fibrocavernous pulmonary tuberculosis.

The aim of the investigation was to determine the characteristics of the immune response regulation for pulmonary tuberculosis (TB) and to analyze the role of regulatory T cells in the immunopathogenesis of TB with eosinophilia in the blood, depending on the clinical form of the disease and sensitivity of Micobacterium tuberculosis to anti-TB drugs.Materials and methods. 157 patients who were initially diagnosed with infiltrative and disseminated TB were examined. The material of the study was venous blood and culture of mononuclear leukocytes isolated from venous blood. The content of interleukin (IL) 4, IL-10 and transforming factor beta (TGFβ) in culture suspensions of mononuclear leukocytes in vitro and IL-5 in the blood was determined by enzyme-linked immunosorbent assay (ELISA) test. The expression of surface molecules CD4, CD20, CD25 and intracellular transcription factor Foxp3 by lymphocytes of the blood was evaluated by flow cytometry. The obtained results were analyzed by statistical methods.Results. It is shown that excessive generation of regulatory T cells in patients with TB is associated with eosinophilia of the blood and imbalance of immune response regulation mechanisms. In TB with eosinophilia, an increase in the number of Foxp3-positive regulatory T cells in the blood is combined with in vitro hypersecretion of anti-inflammatory cytokines TGFβ, IL-10, IL-4 and an increase in the content of CD20+ B lymphocytes and IL-5 in the blood. These changes are most pronounced in the disseminated form of TB in combination with drug resistance.Conclusion. Characteristics of immunoregulation at TB with blood eosinophilia are associated with activation of immunosuppression mechanisms and polarization of immune response towards Th2-dependent pathway.