Evaluation of TNF-α, IL-10 and IL-6 Cytokine Production and Their Correlation with Genotype Variants amongst Tuberculosis Patients and Their Household Contacts

Abstract

BackgroundHousehold 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.ObjectiveThe 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.MethodsThe 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).ResultsThe 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.ConclusionLarge 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.

Use of Molecular Probes for Presumptive Diagnosis of Tuberculosis Associated with Mycobacterium Tuberculosis and Mycobacterium Bovis Infection in Antelopes in Pakistan

“…All the infected animals had greater values of IFN-γ as compare to TNF-α. This may be explained by the major role of IFN-γ in pathogenesis of bovine tuberculosis in contrast to humans that normally have increased TNF-α (Joshi et al, 2015). Another reason for increased IFN-γ as compare to TNF-α may be initial priming of macrophages by IFN-γ to secrete more TNF-α post-infection.…”

Relationship of bovine <i>TNF-α</i> gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle

“…The AG genotype of the rs1800629 SNP showed high levels of the TNF-α protein in serum in active pulmonary tuberculosis patients when compared with healthy controls. The association between the SNPs and their cytokine production indicate the functional importance of cytokines in gene expression [ 18 ]. The rs1800630 SNP (an adenine to cytosine nucleotide change) appears to be associated with an increase in the lung function tests considering a ratio of forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) was identified [ 31 ].…”

“…Possible evolutionary selection pressure appears to affect TNF-α gene expression rather than protein structure, a common finding among the tuberculosis susceptibility genes, as regulation of gene expression may be a prevalent selection mechanism in evolution. Evaluation of the cytokines and any of their inherent polymorphisms might provide a useful diagnostic tool in evaluating immune regulation and progression of the disease [ 18 ]. Hence, we hypothesized that any variation in exon 3 of the bovine TNF-α gene that results in a protein sequence change may influence the relative levels of normal and alternatively TNF-α products.…”

Infection of Monocytes From Tuberculosis Patients With Two Virulent Clinical Isolates of Mycobacterium tuberculosis Induces Alterations in Myeloid Effector Functions

“…Proinflammatory cytokines, including IL-1β, IL-1α, IL-6, IL-8, and TNF-α, are responsible for both the protection and pathogenesis of the human host with active TB. Elevated levels of TNF-α, IL-1β, and IL-6 may be responsible for exaggerated inflammation and the deleterious effects associated with TB (Flynn et al, 2011;Joshi et al, 2015). Spontaneous production of these proinflammatory cytokines by monocytes was observed in active TB (Toossi et al, 1995), and associated with activation of monocytes in vivo due to circulating mycobacterial products, which may be dependent on the severity status of the disease (Barnes et al, 1992;Dlugovitzky et al, 1995;Sethna et al, 1998;Banerjee et al, 2003).…”