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Clinical & Experimental Allergy

Influence of different dosage schedules of inhaled fluticasone propionate on peripheral blood cytokine concentrations in childhood asthma

Authors


H. F. Kauffman, University Hospital Groningen, Department of Allergology, PO Box 30.001, 9700 RB Groningen, the Netherlands. E-mail: h.f.kauffman@path.azg.nl

Summary

Background Asthma is characterized by eosinophilic airways inflammation with elevated levels of IL-4, IL-5 and sICAM-1, and reduced levels of IL-10 and IFN-γ. Inhaled corticosteroids powerfully reduce airways inflammation.

Objective To investigate if eosinophil counts, serum eosinophilic cationic protein (ECP) and sICAM-1 levels, as well as serum and production of cytokines (IL-4, IL-5, IL-10, IFN-γ) by peripheral blood monocytes (PBMCs) are useful markers to monitor therapy with inhaled fluticasone propionate (FP) in asthmatic children.

Methods In a double-blind, 1-year study, 55 asthmatic children (aged 6–10 years) stopped inhaled corticosteroids for a mean period of 24 days and were randomized to receive either FP 200 µg/day (constant dose group), or a starting dose of FP 1000 µg/day with two monthly reductions to 500, 200 and 100 µg/day (stepdown group). Hyper-responsiveness, symptom scores and blood sampling were performed at 2-month intervals.

Results Symptoms and hyper-responsiveness improved significantly in both treatment groups after reintroduction of FP. Eosinophil counts decreased significantly more during the first 2 months of FP in the stepdown group than in the constant dose group (P = 0.03). We found a trend towards a dose-dependent response in changes of eosinophil counts and serum ECP levels during treatment. Serum IL-4 and IL-5 levels were undetectable in the majority of children. No significant effect of the dose of FP on the release of IL-4, IL-5, IL-10 or IFN-γ by Con A stimulated PBMCs was found. sICAM-1 levels did not significantly differ at any time point between the two groups.

Conclusion Serum ECP as well as peripheral blood eosinophils, cytokine production by PBMCs and sICAM-1 levels are insensitive markers in titrating and monitoring therapy with inhaled corticosteroids over a wide dose range in childhood asthma.

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