Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 167, Issue 11, Pages 1516-1521Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200210-1207OC
Keywords
corticosteroid; matrix metalloproteinase; emphysema
Categories
Funding
- NHLBI NIH HHS [1R01 HL60913-01] Funding Source: Medline
Ask authors/readers for more resources
Previous investigations have shown that corticosteroids affect the development and maturation of the developing lung in utero and in neonatal animals. Systemic corticosteroids are routinely used for the treatment of acute exacerbations of chronic obstructive pulmonary disease, and inhaled corticosteroids are more frequently being prescribed for the long-term treatment of patients with chronic obstructive pulmonary disease. Because corticosteroids can affect matrix metalloproteinases and because the concept of protease/antiprotease imbalance is an important concept regarding the pathogenesis of emphysema, we examined the effects of chronic steroid treatment on lung structure in adult rats. Rats treated with 2 mg/kg of methylprednisolone daily for 1, 2, or 4 weeks had an increased mean linear intercept and a decrease of the surface-volume ratio when compared with age-matched control animals, and the animals showed increased matrix metalloproteinase-9 activity in their lungs on zymography. Rats treated concomitantly with methylprednisolone and a broad-spectrum matrix metalloproteinase inhibitor (GM6001) did not develop emphysema. We conclude that systemic treatment of adult rats with the antiinflammatory steroid methylprednisolone increases the activity of matrix metalloproteinases in the lung and causes emphysema.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available