Doxycycline May Treat Toluene Diisocyanate-Induced Asthma
Kathi
By Megan Rauscher
NEW YORK (Reuters Health) Jun 21 - In a murine model of toluene
diisocyanate (TDI)-induced asthma, treatment with doxycycline before
and after exposure reduces airway inflammation and
hyperresponsiveness, researchers from South Korea report in the
Journal of Allergy and Clinical Immunology for May.
This study suggests that doxycycline is a "potentially powerful
therapeutic agent" for TDI-induced asthma, a leading cause of
occupational asthma, Dr. Yong C. Lee from Chonbuk National University
Medical School, in Jeonju, told Reuters Health.
In earlier work, Dr. Lee's team noted that release of the proteolytic
enzyme matrix metalloproteinase-9 (MMP-9) is upregulated in
association with the buildup of inflammatory cells in the airways of
mice with TDI-induced asthma and that inhibiting MMP-9 "may be a good
therapeutic strategy."
To investigate further, Dr. Lee and colleagues force-fed mice the
MMP-inhibiting antibiotic doxycycline (20 mg/kg/day) 6 times at
24-hour intervals on days 35 to 40, beginning 3 days before TDI
challenge. Separately, they tested the effects of MMP inhibitors
administered intraperitoneally 3 times at 24-hour intervals beginning
30 minutes before TDI challenge.
They found that doxycycline and MMP inhibitors curbed "not only MMP-9
activity in the lungs but also the migration of inflammatory cells
through the endothelial and epithelial basement membrane."
"Without these inflammatory cells, the other pathologic changes do not
occur," they write. "Administration of doxycycline," Dr. Lee said,
"reduced all asthmatic pathophysiological features" observed in the
lungs of mice with TDI-induced asthma, namely airway inflammation,
airway hyperresponsiveness, and increased expression of MMP-9.
Results of Western blotting showed that the effects of doxycycline are
mediated through the phosphatidylinositol 3-kinase pathway/Akt,
consistent with prior studies. "Increased phosphorylated-Akt but not
Akt protein levels in lung tissues after TDI inhalation were
significantly reduced by the administration of doxycycline," Dr. Lee
said.
J Allergy Clin Immunol 2004;113:902-909.
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