Matrix metalloproteinases-7, -8, -9 and TIMP-1 in the follow-up of diisocyanate-induced asthma.
BACKGROUND
Diisocyanate-induced asthma (DIA) is known to be associated with poor prognosis. We wished to clarify if matrix metalloproteinases (MMP)-7, -8 or -9 or tissue inhibitor of matrix metalloproteinases (TIMP-1) are associated with the functional or inflammatory outcome in DIA patients.


METHODS
This is a longitudinal study where 17 patients with DIA diagnosed by a specific challenge test to diisocyanates were monitored. Exposure to diisocyanates was terminated seven (mean) months before the challenge test. The studies included spirometry, histamine challenge test and bronchoscopy. MMP-7, MMP-8, TIMP-1 [Enzyme-linked immunosorbent assay (ELISA)- and immunofluorometric assay-methods], MMP-9 (ELISA and zymography), interferon-gamma, tumour necrosis factor-alpha, interleukin-6, -8, -15, -17, CXCL-5/ENA-78, monocyte chemoattractant protein-1 and macrophage inhibitory factor (MIF) (ELISA) were assayed from bronchoalveolar lavage (BAL) fluid. Inhaled steroid therapy was initiated after the examinations, which were repeated at 6 months and at 3 years during the treatment. The results were compared with those of 15 healthy controls.


RESULTS
Inhaled steroid medication increased BAL levels of MMP-9 and MMP-9/TIMP-1 and decreased MMP-7 and MMP-7/TIMP-1. The increase in MMP-9 levels was associated with a decline in the TH-2 type inflammation.


CONCLUSIONS
Our data suggest that reduced TH-2 type inflammation in DIA after inhaled steroid medication is reflected as elevated MMP-9 and MMP-9/TIMP-1 levels in BAL. MIF may be the inducer of MMP-9. This might point to some protective role for MMP-9 in DIA.
Laboratory of Clinical Physiology, Helsinki University Hospital, Helsinki, Finland.
P
P
Piirilä
A
A
Lauhio
M-L
ML
Majuri
A
A
Meuronen
M
M
Myllärniemi
T
T
Tervahartiala
K
K
Vuorinen
A
A
Laitinen
H
H
Alenius
V L
VL
Kinnula
T
T
Sorsa
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D012129:Respiratory Function Tests; D012307:Risk Factors; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D019715:Tissue Inhibitor of Metalloproteinase-1; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9