ABSTRACT
BACKGROUND & OBJECTIVES: Cytokine gene polymorphisms may alter Th1/Th2 balance with major implications in tuberculosis. The aim of our study was to find out whether Interferon gamma +874A and IL-4 -590T polymorphisms were associated with susceptibility to pulmonary tuberculosis as well as the level of IFNgamma and IL-4 in south Indian population. METHODS: Interferon gamma +874A and IL-4 -590T promoter polymorphisms were studied in 129 pulmonary tuberculosis (PTB) patients and 127 normal healthy subjects (NHS) and were associated with culture filtrate and live Mycobacterium tuberculosis induced IFNgamma and IL-4 production in peripheral blood mononuclear cells (PBMCs). IL-4 gene variants were also associated with IgG antibody levels against M. tuberculosis culture filtrate antigen. RESULTS: The variant IFNgamma genotypes and IFNgamma levels between genotypes did not differ significantly in patients and controls. Significantly increased frequency of variant IL-4 'CT' genotype in PTB patients (P<0.05) and 'CC' genotype in control group (P<0.01) was observed. IL-4 levels were detectable in very few subjects and the IgG levels did not differ between the three IL-4 genotypes. INTERPRETATION & CONCLUSION: The study suggests a lack of functional association of Interferon gamma +874A polymorphism in tuberculosis in south Indian population. The higher frequency of IL-4 'CT' genotype in PTB suggests a possible association of IL-4 -590T promoter polymorphism with susceptibility to tuberculosis, and the 'CC' genotype may be associated with protection.
Subject(s)
Adult , Base Sequence , Case-Control Studies , DNA Primers/genetics , Female , Genetic Variation , Humans , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Polymorphism, Single Nucleotide , Tuberculosis, Pulmonary/geneticsABSTRACT
BACKGROUND & OBJECTIVES: Perforin is one of the major effector molecules of cytotoxic cells associated with killing of cells harbouring intracellular bacterial infection. The precise role of perforin positive cells in tuberculosis still remains controversial. The present study was done to determine the number of circulating CD4(+) and CD8(+) perforin positive cells to assess the level of cytotoxic response against Mycobacterium tuberculosis in patients with pulmonary tuberculosis. METHODS: Intracellular perforin and surface CD4 and CD8 staining of peripheral blood lymphocytes was done using specific monoclonal antibodies and enumerated using flowcytometry. RESULTS: A significantly decreased total lymphocytes (P<0.01), CD4 (P<0.001) and CD8 (P<0.01) lymphocyte counts in PTB patients was observed compared to normal healthy individuals (NHS). Intracellular perforin staining showed significantly elevated percentages of total (P<0.05) and CD8 (P<0.01) perforin positive cells in PTB patients compared to NHS. However, the absolute counts of total, CD4 and CD8 cells positive for perforin were similar in patients and NHS. INTERPRETATION & CONCLUSION: Our results suggest that during active stage of pulmonary tuberculosis there was an increased percentage of CD8 cells positive for perforin, irrespective of their absolute counts. Further, CD8(+) perforin positive cells may have increased cytolytic activity against M. tuberculosis in active pulmonary tuberculosis.