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.
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.
Authors: Rodrigo Ribeiro-Rodrigues; Tatiana Resende Co; John L Johnson; Fabiola Ribeiro; Moises Palaci; Ricardo T Sá; Ethel L Maciel; Fausto E Pereira Lima; Valderio Dettoni; Zahra Toossi; W Henry Boom; Reynaldo Dietze; Jerrold J Ellner; Christina S Hirsch Journal: Clin Diagn Lab Immunol Date: 2002-07
Authors: Keertan Dheda; Tawanda Gumbo; Neel R Gandhi; Megan Murray; Grant Theron; Zarir Udwadia; G B Migliori; Robin Warren Journal: Lancet Respir Med Date: 2014-03-24 Impact factor: 30.700
Authors: Ah Young Leem; Joo Han Song; Eun Hye Lee; Hyejon Lee; Bora Sim; Song Yee Kim; Kyung Soo Chung; Eun Young Kim; Ji Ye Jung; Moo Suk Park; Young Sam Kim; Joon Chang; Young Ae Kang Journal: Sci Rep Date: 2018-01-18 Impact factor: 4.379