Matrix metalloproteinase expression and abnormal lung permeability are important determinants of outcome in IPF

¹ Respiratory Medicine Research Group, The Queen's University of Belfast
² Lung Injury and Fibrosis Treatment Programme, Dept of Medical Sciences, Medical School, University of Birmingham

^* To whom correspondence should be addressed. E-mail: d.thickett{at}bham.ac.uk.

	Abstract

Matrix metalloproteinases (MMP) degrade all the extracellular matrix components of the intersititium and may play a role in abnormal alveolar permeability which is a feature of idiopathic pulmonary fibrosis (IPF). This study aimed to evaluated the levels of MMP protein levels in patients with IPF and determine any relationship to treatment and markers of permeability.

20 patients with IPF and 8 controls underwent bronchoalveolar lavage. MMP, TIMP, and VEGF levels were related to clinical outcome and protein permeability index

MMP 3, 7, 8 and 9 were elevated in IPF lavage fluid and levels remain high despite treatment. Levels of MMP-3, 7, 8 and 9, VEGF and protein permeability index were higher in those who died early during follow-up. VEGF, MMP-8 and 9 were higher in those with a rapidly declining lung function over 1 year. Levels of MMP 3, 7, 8 and 9 correlated with an increased permeability index.

MMP levels are elevated in IPF patients and are not modulated by current standard treatment. MMP production through an interaction with the known vascular permogen, VEGF, is potentially associated abnormal capillary permeability and may potentiate the neoangiogenesis seen in IPF. These changes were greatest in those who died or progressed during follow-up suggesting that drugs targeting VEGF or MMP activity warrant assessment as novel therapy for IPF