Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis

Seok Yong Eum, Ye Jin Lee, Jin Hong Min, Hyun Kyung Kwak, Min Sun Hong, Ji Hye Kong, Soo Hee Hwang, Seung Kyu Park, Jason J. Leblanc, Laura E. Via, Clifton E. Barry, Sang Nae Cho

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16 Citations (Scopus)

Abstract

Background: We have previously reported that TNF-α levels correlate to total mycobacterial burden in tuberculosis (TB) patients. Objective: To characterize the dynamics of cytokine responses in TB patients during chemotherapy to identify potential surrogate markers for effective treatment. Methods: Following induction by culture filtrate proteins in whole blood, production patterns of TNF-α, IL-10, IFN-γ and IL-12 were measured in 23 non-multidrug-resistant (MDR)-TB and 16 MDR-TB patients and in 31 healthy controls. Rates of mycobacterial clearance from the sputum were then measured and compared. Results: Prior to the initiation of chemotherapy, TNF-α and IL-10 levels were significantly higher in TB patients than in healthy controls while IFN-γ and IL-12 levels were similar. During chemotherapy, the levels of all 4 cytokines increased. We evaluated these responses separately in patients that did and did not clear their sputum culture at 2 and 6 months. At 2 months, decreases in both IFN-γ and IL-12 correlated strongly with a successful early response, while after 6 months of therapy, when half (7/14) of MDR-TB patients were still sputum culture positive, downregulation of TNF-α was uniquely correlated with sputum conversion between the groups. Conclusion: Our findings suggest the possibility that the regulation of TNF-α production in whole blood may be a more specific indicator of sputum conversion at 6 months than IFN-γ, IL-12 or IL-10 in MDR-TB patients.

Original languageEnglish
Pages (from-to)275-284
Number of pages10
JournalRespiration
Volume80
Issue number4
DOIs
Publication statusPublished - 2010 Sep 1

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

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    Eum, S. Y., Lee, Y. J., Min, J. H., Kwak, H. K., Hong, M. S., Kong, J. H., Hwang, S. H., Park, S. K., Leblanc, J. J., Via, L. E., Barry, C. E., & Cho, S. N. (2010). Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis. Respiration, 80(4), 275-284. https://doi.org/10.1159/000283687