Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify if IFNG, IL12B, TNF, IL17A, IL10, and TGFB1 gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB) at different time points of antituberculosis treatment (T1, T2, and T3). Our results showed the following associations: IFNG +874 T allele and IFNG +2109 A allele with higher IFN-γ levels; IL12B +1188 C allele with higher IL-12 levels; TNF ？308 A allele with higher TNF-α plasma levels in controls and mRNA levels in PTB patients at T1; IL17A A allele at rs7747909 with higher IL-17 levels; IL10 ？819 T allele with higher IL-10 levels; and TGFB1 +29 CC genotype higher TGF-β plasma levels in PTB patients at T2. The present study suggests that IFNG +874T/A, IFNG +2109A/G, IL12B +1188A/C, IL10 ？819C/T, and TGFB1 +21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment. 1. Introduction Mycobacterium tuberculosis (M. tuberculosis) is an intracellular obligate aerobic pathogen which has a predilection for the lungs [1]. Macrophages initiate phagocytosis of M. tuberculosis bacilli and regulate immune responses mediated by proinflammatory cytokines such as TNF-α. Effector T lymphocytes (T cells) and natural killer (NK) cells secrete IFN-γ which activate alveolar macrophages to produce reactive intermediates from nitrogen and oxygen, inhibiting growth and promoting mycobacteria death [2]. IL-12, produced mainly by macrophages and dendritic cells, has a key role in the immune response to M. tuberculosis, bridging innate and adaptive immunity. Moreover, IL-12 induces T cells and NK cells to produce proinflammatory cytokines such as IFN-γ and TNF-α while also regulating the production of IL-17 [2, 3]. A synergistic response of IFN-γ, IL-12, TNF-α and IL-17 activates macrophage, stimulating these cells to eliminate the intracellular pathogen, acting as a major effector mechanism of the cellular immune response [4]. Despite the protective effect of Th1 responses against M. tuberculosis, certain cytokines, such as TNF-α, are correlated with the immunopathogenesis of the disease [5]. To prevent tissue damage, active tuberculosis is associated with decreased Th1 and increased production and action of suppressing cytokines
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