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. 2010;80(4):275-84. doi: 10.1159/000283687. Epub 2010 Feb 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antitubercular Agents / therapeutic use*
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-12 / blood
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / isolation & purification*
  • Sputum / microbiology*
  • Tuberculosis, Multidrug-Resistant / blood*
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tumor Necrosis Factor-alpha / blood*
  • Young Adult

Substances

  • Antitubercular Agents
  • Biomarkers
  • IL10 protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma