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Analysis of Toll-like receptors, iNOS and cytokine profiles in patients with pulmonary tuberculosis during anti-tuberculosis treatment.

de Oliveira LR, Peresi E, Golim Mde A, Gatto M, Araújo Junior JP, da Costa EA, Ayres JA, Fortes MR, Calvi SA - PLoS ONE (2014)

Bottom Line: IL-12 and IFN-γ levels increased after the start of treatment, whereas TNF-α levels were reduced.IL-10 and IL-17 expression and production tended to increase during treatment. iNOS gene expression was reduced throughout treatment in patients.Our results suggest that anti-tuberculosis treatment modulates the immune response, inducing an increase in the expression of TLRs and pro- and anti-inflammatory cytokines to combat bacteria and reduce the inflammatory process.

View Article: PubMed Central - PubMed

Affiliation: Tropical Diseases Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.

ABSTRACT
Toll-like receptors (TLRs) play an important role in mycobacterial infection, although little is known about the roles of these receptors, cytokines and nitric oxide during anti-tuberculosis treatment. Our objective was to evaluate the mRNA and cell surface expression of TLR2 and TLR4; inducible nitric oxide synthase (iNOS) expression; and cytokine Th1, Th2 and Th17 profiles in pulmonary tuberculosis patients at different time points of anti-tuberculosis treatment. Peripheral blood mononuclear cells (PBMCs) were obtained from PPD(+) healthy controls and from patients receiving anti-tuberculosis treatment. Gene expression quantification was performed by qPCR, cell surface expression was assessed using flow cytometry, and cytokine quantification was conducted using the CBA technique. The treated patients presented higher gene expression and higher numbers of receptors on the cell surface of lymphocytes and monocytes than did control individuals. IL-12 and IFN-γ levels increased after the start of treatment, whereas TNF-α levels were reduced. TGF-β presented the highest levels during treatment. IL-10 and IL-17 expression and production tended to increase during treatment. iNOS gene expression was reduced throughout treatment in patients. Our results suggest that anti-tuberculosis treatment modulates the immune response, inducing an increase in the expression of TLRs and pro- and anti-inflammatory cytokines to combat bacteria and reduce the inflammatory process.

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Expression and production cytokines inflammatory.mRNA expression and production of IL-12 (A, B), IFN-γ (C, D), TNF-α (E, F) and IL-17 (G, H) in the control group (G1) and in the patient group during anti-tuberculosis treatment (G2) and at M1 (up to one month of treatment), M2 (three months of treatment) and M3 (end of treatment). The results are expressed as the mean and standard deviation and are representative of three independent replicates. *p<0.05 compared with G1; #p<0.05 compared with M1.
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pone-0088572-g003: Expression and production cytokines inflammatory.mRNA expression and production of IL-12 (A, B), IFN-γ (C, D), TNF-α (E, F) and IL-17 (G, H) in the control group (G1) and in the patient group during anti-tuberculosis treatment (G2) and at M1 (up to one month of treatment), M2 (three months of treatment) and M3 (end of treatment). The results are expressed as the mean and standard deviation and are representative of three independent replicates. *p<0.05 compared with G1; #p<0.05 compared with M1.

Mentions: In TB patients, IL-12 mRNA expression and production tended to increase during treatment. Significantly higher levels of mRNA expression were detected at M2 and M3 (p = 0.005 and p = 0.001, respectively) in relation to expression in controls. Increased IL-12 production levels were observed in TB patients at M2 and M3 (p<0.0001 and p = 0.0009, respectively) in relation to controls (Figures 3A and B).


Analysis of Toll-like receptors, iNOS and cytokine profiles in patients with pulmonary tuberculosis during anti-tuberculosis treatment.

de Oliveira LR, Peresi E, Golim Mde A, Gatto M, Araújo Junior JP, da Costa EA, Ayres JA, Fortes MR, Calvi SA - PLoS ONE (2014)

Expression and production cytokines inflammatory.mRNA expression and production of IL-12 (A, B), IFN-γ (C, D), TNF-α (E, F) and IL-17 (G, H) in the control group (G1) and in the patient group during anti-tuberculosis treatment (G2) and at M1 (up to one month of treatment), M2 (three months of treatment) and M3 (end of treatment). The results are expressed as the mean and standard deviation and are representative of three independent replicates. *p<0.05 compared with G1; #p<0.05 compared with M1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928236&req=5

pone-0088572-g003: Expression and production cytokines inflammatory.mRNA expression and production of IL-12 (A, B), IFN-γ (C, D), TNF-α (E, F) and IL-17 (G, H) in the control group (G1) and in the patient group during anti-tuberculosis treatment (G2) and at M1 (up to one month of treatment), M2 (three months of treatment) and M3 (end of treatment). The results are expressed as the mean and standard deviation and are representative of three independent replicates. *p<0.05 compared with G1; #p<0.05 compared with M1.
Mentions: In TB patients, IL-12 mRNA expression and production tended to increase during treatment. Significantly higher levels of mRNA expression were detected at M2 and M3 (p = 0.005 and p = 0.001, respectively) in relation to expression in controls. Increased IL-12 production levels were observed in TB patients at M2 and M3 (p<0.0001 and p = 0.0009, respectively) in relation to controls (Figures 3A and B).

Bottom Line: IL-12 and IFN-γ levels increased after the start of treatment, whereas TNF-α levels were reduced.IL-10 and IL-17 expression and production tended to increase during treatment. iNOS gene expression was reduced throughout treatment in patients.Our results suggest that anti-tuberculosis treatment modulates the immune response, inducing an increase in the expression of TLRs and pro- and anti-inflammatory cytokines to combat bacteria and reduce the inflammatory process.

View Article: PubMed Central - PubMed

Affiliation: Tropical Diseases Department, Botucatu School of Medicine - UNESP, Botucatu, São Paulo, Brazil.

ABSTRACT
Toll-like receptors (TLRs) play an important role in mycobacterial infection, although little is known about the roles of these receptors, cytokines and nitric oxide during anti-tuberculosis treatment. Our objective was to evaluate the mRNA and cell surface expression of TLR2 and TLR4; inducible nitric oxide synthase (iNOS) expression; and cytokine Th1, Th2 and Th17 profiles in pulmonary tuberculosis patients at different time points of anti-tuberculosis treatment. Peripheral blood mononuclear cells (PBMCs) were obtained from PPD(+) healthy controls and from patients receiving anti-tuberculosis treatment. Gene expression quantification was performed by qPCR, cell surface expression was assessed using flow cytometry, and cytokine quantification was conducted using the CBA technique. The treated patients presented higher gene expression and higher numbers of receptors on the cell surface of lymphocytes and monocytes than did control individuals. IL-12 and IFN-γ levels increased after the start of treatment, whereas TNF-α levels were reduced. TGF-β presented the highest levels during treatment. IL-10 and IL-17 expression and production tended to increase during treatment. iNOS gene expression was reduced throughout treatment in patients. Our results suggest that anti-tuberculosis treatment modulates the immune response, inducing an increase in the expression of TLRs and pro- and anti-inflammatory cytokines to combat bacteria and reduce the inflammatory process.

Show MeSH
Related in: MedlinePlus