Regulation of stromal cell-derived factor-1 and exhaled nitric oxide in asthmatic children following montelukast and ketotifen treatment.
BACKGROUND
Montelukast and ketotifen are oral anti-allergy medications in asthmatic children. This study investigates the modulation effect of montelukast and ketotifen on children with intermittent to mild persistent asthma as demonstrated by the levels of peak expiratory flow (PEF), asthma scores (AS), exhaled nitric oxide (eNO) and plasma stromal cell-derived factor-1 (SDF-1) concentration in a randomized, prospective study.


METHODS
Fifty asthmatic children were enrolled and received 8 weeks of treatment with oral montelukast sodium 5mg chewable tablet administered once daily, or 1mg ketotifen, and were followed for a 4-week post-treatment washout period. ENO concentration, AS and PEF were measured before, 2, 4, 6 and 8 weeks after initial treatment, and 4 weeks after cessation of treatment.


RESULTS
Montelukast therapy was showed to improve AS, PEF and eNO within 2 weeks and remained the improvement during the treatment period. Montelukast also significantly decreased plasma SDF-1 levels after 8 weeks of treatment. In contrast, the ketotifen treatment revealed no significant effects in these clinical parameters until 4 and 6 weeks of the therapy, and did not suppress plasma SDF-1 levels after 8 weeks of treatment. To prove whether montelukast directly suppressed SDF-1 induction, we studied effects of montelukast on the LPS-induced SDF-1 expression and SDF-1-induced chemotaxis of monocytic (THP-1) cells. Montelukast, but not ketotifen, could suppress SDF-1 expression and its related chemotaxis on THP-1 monocytic cells.


CONCLUSIONS
Leukotriene receptor antagonist, such as montelukast, may be a better non-steroid anti-inflammatory drug for mild childhood asthma in preventing airway inflammation.
Hung
Chih-Hsing
CH
Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University, Taiwan, ROC. pedhung@hotmail.com
Jong
Yuh-Jyh
YJ
Hua
Yi-Ming
YM
Li
Chi-Yuan
CY
Lai
Yuan-Sheng
YS
Yang
Kuender D
KD
Chang
Hui-Chiu
HC
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D019819:Budesonide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood*; D002633:Chemotaxis / Q000187:drug effects; D002648:Child; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D045853:Exhalation; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007665:Ketotifen / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011446:Prospective Studies; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D013440:Sulfides
D000085:Acetates; D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003521:Cyclopropanes; D005419:Flavonoids; D011804:Quinolines; D013440:Sulfides; D009569:Nitric Oxide; D019819:Budesonide; C093875:montelukast; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium; D007665:Ketotifen