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.

Vitamin D, an immunomodulator of macrophage function, can activate human antimycobacterial activity. Vitamin D deficiency (VDD) is associated with an impaired mycobacterial immunity and susceptibility to tuberculosis. It has been found that vitamin D and its receptor may be essential for immune function. In this study, we examined the serum 25(OH) vitamin D levels and its receptor (VDR) polymorphisms with susceptibility to tuberculosis in patients, household contacts and healthy controls. Serum 25(OH) vitamin D levels were measured in 75 cases (25 patients, 25 household contacts and 25 healthy controls), and polymorphisms (BsmI and FokI) were carried out in 335 cases (110 patients, 110 household contacts and 115 healthy controls). The proportion of serum 25(OH) vitamin D deficiency and insufficiency was high in patients (44, 58%) and household contacts (40, 48%) compared to controls (48%). The BB and Bb genotypes of BsmI were significantly associated in patients (P < 0.014; OR: 0.509; CI: 0.265-0.876) (P < 0.001; OR: 2.351; CI: 1.368-4.041) and household contacts (P < 0.04; OR: 0.575; CI: 0.336-0.985); (P < 0.002; OR: À2.267; CI: 1.32-3.895) when compared to healthy controls. The diplotype and MDR analysis showed the high-risk genotypes of BsmI and FokI polymorphisms. Vitamin D deficiency and its association with VDR gene polymorphisms may be useful to identify the high-risk group individuals.

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Cytokine gene polymorphisms are known to be associated with functional differences in cytokine regulation and may affect host susceptibility to tuberculosis (TB). Contacts are important group in developing tuberculosis infection and are 10–60 times more likely to develop TB than general population. The present study was carried out in patients with TB (N = 176), their household contacts (HHC; N = 155) from Free Chest TB Clinic PPM DOTS (1TU) covering 500,000 population at Mahavir Hospital and Research Centre, Hyderabad, and healthy controls (HC; N = 170) also included. The association of single‐nucleotide polymorphisms (SNPs) in the promoter region of TNF‐α (−308G/A), IL‐2 (−330T/G), IL‐4 (−589C/T) and in exon region of TGF‐β1 (+869T/C) genes was assessed by ARMS & PCR‐RFLP using specific primers in the above‐mentioned subjects. The differences in allelic or genotypic frequencies of TNF‐α (−308G/A) between patients, their HHC and HC were not statistically significant (P > 0.05). IL‐2 (−330T/G) TG genotype was significantly different between patients, HHC compared to HC (P < 0.002, OR‐1.997, 95%CI‐1.260‐3.168, P < 0.03, OR‐1.602, 955CI‐1.003‐2.561).IL‐4 (−589C/T) CC genotype was significantly different between patients and HC (P < 0.03, OR‐1.791, 95%CI‐1.009‐3.189) as well as between HHC and HC at P < 0.0001, OR‐2.56, 95%CI‐1.448‐4.545. In addition, the TGF‐β 1 (+869T/C) TC genotype was significantly associated with susceptibility to tuberculosis in patients when compared against HC(P < 0.0001, OR‐3.416, 95%CI‐2.063‐5.670) and HHC (P < 0.0001, OR‐2.357, 95%CI‐1.439‐3.868), respectively.MDR analysis indicated that TT genotype of TGF‐β1 with TT and CT genotypes of IL‐4 showed high risk with GA, TT genotypes of TNF‐α, IL‐2, respectively. Our results suggest that IL‐2 (‐330T/G), IL‐4 (‐589 C/T) and TGF‐β1 (+869T/C) gene polymorphisms may be associated with TB susceptibility.

Chronic Idiopathic Urticaria (CIU) is a common skin disorder, which may occur spontaneously. The aim of the present study was to assess the serum levels of interferon (IFN)-γ and interleukin (IL)-6 and to examine the association of IFN-γ+874 T/A and IL-6-174 G/C cytokine gene polymorphisms. To accomplish this, ELISA-based cytokine serum levels of IFN-γ (n=30) and IL-6 (n=30) in CIU patients (n=100) and Healthy Controls (HC) (n=200) were performed. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed to verify the positional significance. A significant (p<0.0001) increase in the serum cytokine levels of IFN-γ and IL-6 was recorded in CIU patients compared to HC. The AT and TT genotypes of IFN-γ and GG genotype of IL-6 were found to be significantly associated with CIU. In conclusion, our findings show a significant increase in the cytokine levels of IFN-γ and IL-6, highlighting their regulatory role in the development of disease. In addition to this, association studies have revealed that TT genotype of IFN-γ +874 T/A and GG genotype of IL-6-174 G/C were susceptible towards the CIU.