Tuberc Respir Dis.  2002 Oct;53(4):420-430. 10.4046/trd.2002.53.4.420.

Changes of Sputum Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinase-1 by Antibiotic Treatment in Acute Exacerbation of Chronic Bronchitis

• Yoon HK
• Ahn JH
• Kim CH
• Kwon SS
• Kim YK
• Kim KH
• Moon HS
• Park SH
• Song JS

• KMID: 1970599
• DOI: http://doi.org/10.4046/trd.2002.53.4.420

Abstract

BACKGROUND: Excessive extracellular matrix (ECM) deposition by airway inflammation is presumed to play an important role in the pathogenesis of worsening airflow obstruction (Ed- acceptable three-word noun) seen during acute exacerbations of chronic bronchitis. Although many proteases can cleave ECM molecules, matrix metalloproteinases (MMPs) and their inhibitors are likely to be the physiologically relevant mediators of ECM degradation.
OBJECTIVES
The purpose of this study was to demonstrate that antibiotic treatment can change airway MMPs and TIMP-1 concentrations/levels by controlling airway inflammation in acute exacerbation of chronic bronchitis. METHOD: We studied 40 patients, all of whom had an acute exacerbation of chronic bronchitis. The patients were treated with two different antibiotics, moxifloxacin and clarithromycin, in a double-blind manner for 7 days. Sputum samples were induced and collected before and after antibiotic therapy. We measured the sputum concentration of MMP-1,-9, TIMP-1, IL-8 and secretory leukocyte proteinase inhibitor (SLPI) in sputum supernatants by ELISA method.
RESULTS
There was no difference after antibiotic treatment in the sputum concentrations of MMP-1,-9, TIMP-1, IL-8 and SLPI between the patients treated with moxifloxacin and those treated with clarithromycin. But the sputum concentrations of TIMP-1, and SLPI, and the TIMP-1/MMP-1 ratio were significantly reduced by the antibiotic therapy. There were significant positive correlations between sputum TIMP-1 levels and IL-8 levels (p<0.01, r=0.751), and between the sputum TIMP-1/MMP-1 ratio and IL-8 levels (p<0.01, r=0.752). The sputum SLPI levels were significantly elevated by antibiotic treatment and were negatively correlated with sputum TIMP-1 levels (p<0.01, r=-0.496) and TIMP-1/MMP-1 levels (p<0.01, r=-0.456).
CONCLUSION
The study shows that the worsening of airway inflammation in acute exacerbation of chronic bronchitis is associated with an imbalance between the concentrations/levels of TIMP-1 and MMPs. Antibiotic treatment can prevent progression of airway narrowing in acute exacerbation of chronic bronchitis by modulation of the protease and anti-protease imbalance.

Keyword

Chronic bronchitis; Acute exacerbation; Matrix metalloproteinase; Tissue inhibitor of matrix metalloproteinase-1; Antibiotics

MeSH Terms

Anti-Bacterial Agents
Bronchitis, Chronic*
Clarithromycin
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix
Humans
Inflammation
Interleukin-8
Leukocytes
Matrix Metalloproteinase 1*
Matrix Metalloproteinases*
Peptide Hydrolases
Sputum*
Tissue Inhibitor of Metalloproteinase-1
Anti-Bacterial Agents
Clarithromycin
Interleukin-8
Matrix Metalloproteinase 1
Matrix Metalloproteinases
Peptide Hydrolases
Tissue Inhibitor of Metalloproteinase-1