The anti-inflammatory effects of inhaled corticosteroids versus anti-leukotrienes on the lymphocyte P-glycoprotein (PGP) expression in asthmatic children.
BACKGROUND
Inhaled corticosteroids (ICS) are used in asthma therapy for their anti-inflammatory effects. P-glycoprotein (PGP) is a transmembrane efflux pump for many drugs, including corticosteroids. Expression of PGP is associated with therapy resistant disease.


OBJECTIVE
The purpose of this study was to compare expression levels of PGP in blood lymphocytes of pediatric asthma patients either on ICS or on the leukotriene inhibitor montelukast medication.


METHODS
The evaluation of lymphocyte PGP expression was performed on a sample of 99 children (66 boys and 33 girls) aged 2-18 (median 12) years with intermittent or persisting mild asthma, (as defined by GINY 2002). The asthmatic children were divided into 3 groups: (1) treated by ICS budesonide 200-400 microg per day (n = 27) more than 1 year; (2) treated by oral montelukast 4 or 5 mg at an age-based dose (n = 16); and (3) treated by inhaled corticosteroids and montelukast (n = 45). Reference PGP values were obtained from a group of 64 healthy children (23 boys and 29 girls) aged 2-15 years (median, 10 years). The expression of lymphocyte PGP was determined on fixed and permeabilized blood mononuclear cells using indirect immunofluorescence staining technique by flow cytometry modified according to Boer et al., 1997.


RESULTS
Based on the weighted medians for PGP expression in peripheral blood lymphocytes, we found a significant difference (p < 10(-3)) between the group of asthma patients (n = 99), (619 +/- 5.3) and healthy controls (n = 64) (446.9 +/- 4.4). Second, there was a lower level of PGP expression in the group treated by ICS (548.6 +/- 9) than the group treated by montelukast and montelukast with budesonide (643.2 +/- 6.3) (p < 10(-6)).


CONCLUSIONS
The anti-inflammatory activity of ICS is more effective in decreasing the production of pro-inflammatory mediators and results in reduced multidrug resistence (MDR-1) gene activity and expression of lymphocyte PGP in asthmatic children.
Kopriva
Frantisek
F
Medical Faculty, Pediatrics, Olomouc, Czech Republic. koprivaf@fnol.cz
Dzubak
Petr
P
Potesil
Jan
J
Hajduch
Marian
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000085:Acetates / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D001249:Asthma / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D019819:Budesonide / Q000008:administration & dosage*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D020024:Leukotriene Antagonists / Q000008:administration & dosage; D008297:Male; D009330:Nebulizers and Vaporizers; D011336:Probability; D011804:Quinolines / Q000008:administration & dosage*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013440:Sulfides; D013601:T-Lymphocytes / Q000166:cytology; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000085:Acetates; D000305:Adrenal Cortex Hormones; D003521:Cyclopropanes; D018836:Inflammation Mediators; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D019819:Budesonide; C093875:montelukast