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.
Department of Allergy, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland. obaseya@yahoo.co.jp
Y
Y
Obase
P
P
Rytilä
T
T
Metso
A S
AS
Pelkonen
T
T
Tervahartiala
M
M
Turpeinen
M
M
Mäkelä
U
U
Saarialho-Kere
O
O
Selroos
T
T
Sorsa
T
T
Haahtela
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