Metalloproteinases and their inhibitors are influenced by inhalative
glucocorticoid therapy in combination with environmental dust reduction in
equine recurrent airway obstruction
Background Overexpression of matrix-metalloproteinases (MMPs) has been shown
to lead to tissue damage in equine recurrent airway obstruction (RAO), as a
misbalance with their natural inhibitors, the tissue inhibitors of
metalloproteinases (TIMPs), occurs. This favors irreversible pulmonary
fibrosis formation. Increased levels of MMPs, TIMPs or altered ratios between
them can be used as biomarkers of respiratory disease. We hypothesized that
levels of MMPs, TIMPs and their ratios correlate with improvement in clinical
findings and bronchoalveolar lavage fluid (BALF) cytology after 10 days of
inhalative glucocorticoid therapy and environmental dust reduction (EDR) and
may be used to monitor treatment success. Ten horses with a history of RAO
participated in a prospective clinical study. Clinical and cytological scoring
was performed before and after inhalative therapy using budesonide (1500 μg
BID over 10 days) and EDR (bedding of wood shavings and wet hay as roughage).
Gelatin zymography was performed for qualitative and semi-quantitative
evaluation of MMP-2 and MMP-9 in BALF supernatant, while fluorimetry was used
to evaluate MMP-8 activity. Additionally, specific equine ELISA assays were
used for quantitative assessment of MMP-2, MMP-9, TIMP-1 and TIMP-2. Results A
significant reduction in the total and several single parameters of the
clinical score were found after 10 days of inhalative therapy and EDR. The
concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 (ELISA) as well as their
activities (MMP-2 and MMP-9 zymography and MMP-8 fluorimetry) were
significantly decreased after therapy. Significant improvements in
MMP-8/TIMP-1 and MMP-8/TIMP-2 ratios were also found, differences between
other ratios before and after therapy were insignificant. Conclusions
Metalloproteinases and their inhibitors, in particular MMP-9 and TIMP-2, are
valuable markers for clinical improvement in RAO