Circulating MMP-9 and TIMP-1 in acute exacerbations and after remission induced by oral corticosteroids in asthmatic children

Abstract

Background Matrix metalloproteinase-9 (MMP-9) is a collagenase implicated in extracellular matrix (ECM) turnover. Tissue inhibitor of metalloproteinase (TIMP-1) binds MMP-9 to inhibit its proteolytic activity; it also modulates cell proliferation, apoptosis, angiogenesis and the development of irreversible airflow obstruction and remodeling. Objective: To investigate the serum levels of MMP-9, TIMP-1 and IL-8 in asthma exacerbations and convalescence, and the possible effect of oral corticosteroids on them. Methods: Circulating levels of MMP-9 and TIMP-1 were measured using ELISA in 33 children with mean age (7.35 ±2.4 years) experiencing an asthma exacerbation before and after oral corticosteroid therapy and 30 age-matched children with stable asthma. Children were recruited during emergency or routine visits to Pediatric Chest Clinic, Ain Shams University. Circulating MMP-9 and TIMP-1 were correlated to degree of airway obstruction as measured by % decrease in FEV1. Results: In the present study plasma levels of MMP-9 correlated to MMP-9 specific enzyme activity .ٍٍSignificantly higher circulating levels of MMP-9 and TIMP-1 were detected in patients with asthma exacerbations compared to patients with stable asthma. The degree of airway obstruction measured by % decrease in FEV1 correlated positively to both MMP-9 and TIMP-1 levels and correlated negatively to MMP-9/TIMP-1 ratio during acute exacerbations. MMP-9 correlated to blood neutrophil, eosinophil and lymphocyte counts during acute exacerbations. After oral steroids, there was a significant decline in circulating MMP-9. However TIMP-1 did not show significant change. Decrease in MMP-9/TIMP-1 ratio correlated to FEV1 changes. Conclusion: MMP-9 is a serum marker of asthma exacerbations that is correlated to degree of airway obstruction and blood inflammatory cells. Imbalance between MMP-9 and TIMP-1 after asthma exacerbation might contribute significantly to airway remodeling and TIMP-1 production in acute asthma might not be suppressed by corticosteroids. MMP-9 and TIMP-1 might be important targets for therapeutic applications in patients with asthma.

Keywords: Asthma, MMP-9, TIMP-1, Asthma exacerbations, Airway remodeling

Egypt J Pediatr Allergy Immunol 2006; 4(1):23-29