Plasma levels of tumor necrosis factor-alpha, interferon-gamma, inducible nitric oxide synthase, and 3-nitrotyrosine in drug-resistant and drug-sensitive pulmonary tuberculosis patients, Ibadan, Nigeria

摘要

Background: Nigeria is one of the countries with a high burden of tuberculosis (TB) in the world. TB associated inflammation is reported to be central to progression from latent TB to active TB or drug sensitive TB (DSTB) to drug resistant TB (DRTB). Inflammatory cytokines, especially interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), act synergistically in the control of TB infection. They activate macrophages to produce effector molecules such as inducible nitric oxide synthase (iNOS), nitric oxide, and ultimately 3-nitrotyrosines(3-NTs), which are involved in the control of TB. This study investigated the potential involvement of TNF-alpha, IFN-gamma, iNOS, and 3-NT in differentiating DRTB and DSTB in Ibadan, Nigeria. Methods: One hundred participants above 18 years were recruited into this study and were grouped as follows: 32 DRTB, 34 DSTB, and 34 apparently healthy controls. Plasma from the patients was used for the analyses of inflammatory (TNF alpha and IFN-gamma) and oxidative stress (iNOS and 3-NT) biomarkers using the ELISA. Mann-Whitney test was applied for the statistical test. Results: Mean levels of plasma TNF-alpha, IFN-gamma, iNOS, and 3-NT were higher in DRTB (19.74 +/- 3.62 pg/mL, 4.41 +/- 0.96 pg/mL, 1791.07 +/- 419.42 pg/mL, and 20.27 +/- 1.80 ng/mL, respectively) and DSTB (17.02 +/- 1.84 pg/mL, 5.59 +/- 1.40 pg/mL, 2823.42 +/- 685.32 pg/mL, and 25.06 +/- 2.15 ng/mL, respectively) compared with controls (12.18 +/- 0.92 pg/mL, 1.58 +/- 0.21 pg/mL, 1275.86 +/- 166.12 pg/mL, and 19.98 +/- 1.23 ng/mL, respectively). In addition, higher plasma levels of IFN-gamma (P > 0.05), iNOS (P > 0.05), and 3-NT (P < 0.05) were observed in DSTB compared with DRTB patients. Conclusion: The 3-NT may be used as differentiating markers of DSTB from DRTB.