title: 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: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bhagwan Mahavir Medical Research Centre, Hyderabad, India.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Joshi
authors.affiliation: Bhagwan Mahavir Medical Research Centre, Hyderabad, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Ponnana
authors.affiliation: Bhagwan Mahavir Medical Research Centre, Hyderabad, India.
authors.forename: Ramya
authors.initials: R
authors.lastname: Sivangala
authors.affiliation: Department of Transplant Biology & Stem Cell, Global Hospital, Hyderabad, India.
authors.forename: Lakshmi Kiran
authors.initials: LK
authors.lastname: Chelluri
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, India.
authors.forename: Prathiba
authors.initials: P
authors.lastname: Nallari
authors.affiliation: Bhagwan Mahavir Medical Research Centre, Hyderabad, India.
authors.forename: Sitaramaraju
authors.initials: S
authors.lastname: Penmetsa
authors.affiliation: LEPRA India, Blue Peter Public Health & Research Centre, Cherlapally, Hyderabad, India.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Valluri
authors.affiliation: Bhagwan Mahavir Medical Research Centre, Hyderabad, India; Department of Genetics, Osmania University, Hyderabad, India.
authors.forename: Sumanlatha
authors.initials: S
authors.lastname: Gaddam
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D005190:Family; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D012307:Risk Factors; D014376:Tuberculosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10