Induced Sputum MMP-1,-3 &-8 Concentrations during Treatment of Tuberculosis


Ugarte-Gil, CA; Elkington, P; Gilman, RH; Coronel, J; Tezera, LB; Bernabe-Ortiz, A; Gotuzzo, E; Friedland, JS; Moore, DAJ; (2013) Induced Sputum MMP-1,-3 &-8 Concentrations during Treatment of Tuberculosis. PLoS One, 8 (4). ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0061333

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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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: TB Centre
PubMed ID: 23613834
Web of Science ID: 317911500028
URI: http://researchonline.lshtm.ac.uk/id/eprint/989811

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