Background: Household contacts of diagnostically established tuberculosis (TB) patients are highly susceptible to disease development. It is surmised that cytokines perhaps play a synergistic and a prognostic role in the activation of the otherwise latent infection in these house hold contacts. Evaluation of the cytokines and any of their inherent polymorphisms might provide a useful diagnostic tool in evaluating the immune regulation and the progression of the disease. The cytokines thus released in a paracrine manner in serum may also provide an indirect measure of the cytokine function. Objective: The present study was aimed to evaluate the levels of TNF-α, IL-10 & IL-6 cytokines and their correlation with genotype variants amongst tuberculosis patients and their household contacts. Methods: The cytokine levels were estimated in serum by enzyme-linked immunosorbent assay (ELISA) and their polymorphisms were studied by amplification refractory mutation system polymerase chain reaction (ARMs PCR) in active pulmonary tuberculosis patients (APTB = 150), household contacts (HHC = 190), and healthy controls (HC = 150). Results: The median values of TNF-α cytokine were significantly high among APTB and HHC compared to HCs (P< 0.0001 and 0.0001). IL-6 levels also were elevated among APTB compared to HHC and HC, and a significant difference was observed between APTB and HHC at P<0.0001; APTB & HC at P< 0.04; HHC & HC at P< 0.01. The IL-10 levels were low in APTB compared to HHC and HCs and no significant difference was observed. TNF-α/IL-10 ratio was significant and indicated Th1 predominance in APTB and HHC. IL-6/IL-10 showed pronounced Th1 expression in APTB and Th2 in HHC and HC. The ROC analysis indicated that both IL-10 and IL-6 can be used to decide the risk of exposed individual to a disease. The results of multivariate analysis indicate that IL-10 (-1082) GA genotype was significantly associated with p<0.028 in APTB. No significant association was observed between genotypes, other serum cytokine levels and clinical characteristics between APTB, HHC and HCs. Conclusion: Large sample size with follow-up at different time points may further illuminate the role of IL-10 and IL-6 cytokines as a prognostic marker in house hold contacts.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tb), and it remains one of the major bacterial infections worldwide. Innate immunity is an important arm of antimycobacterial host defence mechanism that senses various pathogen‐associated molecular patterns (PAMP) of microbes by a variety of pattern recognition receptors (PRRs). As per the recent discovery, Toll‐like receptors (TLRs) play a crucial role in the recognition of M. tb, this immune activation occurs only in the presence of functional TLRs. Variants of TLRs may influence their expression, function and alters the recognition or signalling mechanism, which leads to the disease susceptibility. Hence, the identification of mutations in these receptors could be used as a marker to screen the individuals who are at risk. In this review, we discuss TLR SNPs and their signalling mechanism to understand the susceptibility to TB for better therapeutic approaches.

Tuberculosis (TB) constitutes the major cause of death due to infectious diseases. Cytokines play a major role in defence against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Household contacts (HHC) are at increased risk of developing the disease. In this study, we examined the association of IL‐1β and IL‐10 cytokine gene polymorphisms with risk of developing tuberculosis in TB patients, their HHC and healthy controls (HC) using JavaStat and SPSS. Multifactor dimensionality reduction (MDR) analyses were performed to explore the potential gene–gene interactions. The genotype and allele frequencies of IL‐1β +3954C/T polymorphism did not vary significantly between TB patients and HC. GG (P < 0.005, OR = 0.219 and 95% CI = 0.059–0.735) and GA (P < 0.0001, OR = 2.938 and 95% CI = 1.526–5.696) genotypes of IL‐10‐1082 G/A polymorphism were found to be significantly associated with patients versus HC. HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1–3.35) genotype in IL‐1β and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225–9.702) genotype in IL‐10 were at increased risk of developing tuberculosis. MDR tests revealed high‐risk genotypes in IL‐1β and IL‐10 based on the association model. Our results demonstrate that the polymorphisms of IL‐1β and IL‐10 genes may be valuable markers to predict the risk for the development of TB in household contacts.