Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children.
BACKGROUND
The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue are poorly characterized in vivo.


METHODS
We compared MMP-8 and TIMP-1 levels in induced sputum and their expression in airway inflammatory cells of healthy children (n = 27) and of children with newly diagnosed asthma with mild (n = 20) or moderate symptoms (n = 19), before and after 6 months of treatment with inhaled budesonide.


RESULTS
At baseline, MMP-8 was higher in asthmatic children with moderate symptoms, TIMP-1 was lower and the MMP-8/TIMP-1 ratio was higher in both groups of asthmatic children compared with controls. Inhaled budesonide increased TIMP-1 levels in both groups of asthmatic children and normalized the MMP-8/TIMP-1 ratio, and this paralleled the improvement in forced expiratory volume in 1 s in children with mild symptoms. At baseline, asthmatic children had significantly more MMP-8-positive macrophages than control children, whereas the number of TIMP-1-positive macrophages was almost the same. Budesonide decreased the percentage of MMP-8-positive macrophages and increased that of TIMP-1-positive macrophages; these changes were significant in asthmatic children with mild symptoms.


CONCLUSIONS
Inhaled budesonide normalized the MMP-8/TIMP-1 ratio in asthmatic children by upregulation of TIMP-1 production and downregulation of MMP-8 production by airway macrophages. This change may be a biochemical marker of an effect on airway inflammation and possibly of an ongoing remodeling process that should be further investigated using biopsy specimens.
Obase
Y
Y
Department of Allergy, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland. obaseya@yahoo.co.jp
Rytilä
P
P
Metso
T
T
Pelkonen
A S
AS
Tervahartiala
T
T
Turpeinen
M
M
Mäkelä
M
M
Saarialho-Kere
U
U
Selroos
O
O
Sorsa
T
T
Haahtela
T
T
D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D019819:Budesonide / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012129:Respiratory Function Tests; D013183:Sputum / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D019819:Budesonide; D020784:Matrix Metalloproteinase 8