title: Induced sputum MMP-1, -3 & -8 concentrations during treatment of tuberculosis.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú. cesar.ugarte@upch.pe
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Ugarte-Gil
authors.forename: Paul
authors.initials: P
authors.lastname: Elkington
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Jorge
authors.initials: J
authors.lastname: Coronel
authors.forename: Liku B
authors.initials: LB
authors.lastname: Tezera
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernabe-Ortiz
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gotuzzo
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
authors.forename: David A J
authors.initials: DA
authors.lastname: Moore
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D046508:Culture Techniques; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D013183:Sputum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*
chemical_list: D000995:Antitubercular Agents; D019714:Tissue Inhibitor of Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D019278:Matrix Metalloproteinase 3; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1