Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = <0.0001, p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.

Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.

Several factors are associated with the development of different clinical forms of tuberculosis (TB). The present study evaluated epidemiological variables and cytokine levels in samples from 89 patients with TB (75 with pulmonary TB and 14 with extrapulmonary TB) and 45 controls. Cytokines were measured by flow cytometry (Human Th1/Th2/Th17 Cytometric Bead Array kit). The TB group had a higher frequency of individuals who were 39 years of age or older, married, with primary education or illiterate and had a lower family income (p < 0.05). All individuals with extrapulmonary TB reported that they were not working, and the main reasons were related to disease symptoms or treatment. The levels of IFN-γ (OR = 4.06) and IL-4 (OR = 2.62) were more likely to be elevated in the TB group (p = 0.05), and IFN-γ levels were lower in patients with extrapulmonary TB compared to those with pulmonary TB (OR = 0.11; p = 0.0050). The ROC curve was applied to investigate the diagnostic accuracy of IFN-γ levels between the different clinical forms of tuberculosis, resulting in high AUC (0.8661; p < 0.0001), sensitivity (93.85%) and specificity median (65.90%), suggesting that IFN-γ levels are useful to differentiate pulmonary TB from extrapulmonary TB. The dysregulation of pro- and anti-inflammatory cytokine levels represent a risk for the development of TB and contribute to the pathogenesis of the disease, especially variation in IFN-γ levels, which may determine protection or risk for extrapulmonary TB.