Induced sputum MMP-1, -3 & -8 concentrations during treatment of tuberculosis

PLoS One. 2013 Apr 22;8(4):e61333. doi: 10.1371/journal.pone.0061333. Print 2013.

Abstract

Introduction: Tuberculosis (TB) destroys lung tissues and this immunopathology is mediated in part by Matrix Metalloproteinases (MMPs). There are no data on the relationship between local tissue MMPs concentrations, anti-tuberculosis therapy and sputum conversion.

Materials and methods: Induced sputum was collected from 68 TB patients and 69 controls in a cross-sectional study. MMPs concentrations were measured by Luminex array, TIMP concentrations by ELISA and were correlated with a disease severity score (TBscore). 46 TB patients were then studied longitudinally at the 2nd, 8th week and end of treatment.

Results: Sputum MMP-1,-2,-3,-8,-9 and TIMP-1 and -2 concentrations are increased in TB. Elevated MMP-1 and -3 concentrations are independently associated with higher TB severity scores (p<0.05). MMP-1, -3 and -8 concentrations decreased rapidly during treatment (p<0.05) whilst there was a transient increase in TIMP-1/2 concentrations at week 2. MMP-2, -8 and -9 and TIMP-2 concentrations were higher at TB diagnosis in patients who remain sputum culture positive at 2 weeks and MMP-3, -8 and TIMP-1 concentrations were higher in these patients at 2nd week of TB treatment.

Conclusions: MMPs are elevated in TB patients and associate with disease severity. This matrix-degrading phenotype resolves rapidly with treatment. The MMP profile at presentation correlates with a delayed treatment response.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Case-Control Studies
  • Cross-Sectional Studies
  • Culture Techniques
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 8 / metabolism
  • Matrix Metalloproteinases, Secreted / metabolism*
  • Sputum / drug effects*
  • Sputum / enzymology
  • Sputum / metabolism*
  • Tissue Inhibitor of Metalloproteinases / metabolism*
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / enzymology
  • Tuberculosis, Pulmonary / metabolism*

Substances

  • Antitubercular Agents
  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinases, Secreted
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 1