Gene expression of interleukin‐3 and granuloeyte maerophage colony‐stimulating factor in circulating CD4+ T cells in acute severe asthma

Abstract

Interleukin (IL)-3 and granulocyte macrophage colony-stimulating factor (GM-CSF) may influence the inflammatory process in asthma through their regulatory role on eosinophil survival, differentiation and effector function. To examine the relationships between IL-3 and GM-CSF messenger (m) ribonucleic acid (RNA) expression in peripheral blood CD4+ cells and serum levels of eosinophil cationic protein (ECP), a marker of eosinophil activation, and disease activity in asthma. Venous blood was drawn from patients with acute severe asthma prior to the commencement of systemic steroid therapy (day 1) and 7 days afterwards (day 7), patients with stable disease and normal healthy volunteers. The capacity for expression of IL-3 and GM-CSF in ex vivo stimulated circulating CD4+ cells was assessed semi-quantitatively by reverse transcription-polymerase chain reaction (RT-PCR). We found that the capacity for expression of IL-3 and GM-CSF was significantly higher in acute asthmatics prior to steroid treatment (n = 24) than those in stable disease (n = 38) and healthy subjects (n = 32, P < 0.001 for IL-3 and < 0.05 for GM-CSF), but no difference was observed between the latter two groups. Further assessment made in 15 of the 24 acute asthmatics 7 days after systemic steroid treatment revealed a significant reduction in GM-CSF expression (P < 0.05) but not for IL-3. At the same time, PEF also improved significantly from 30.4 +/- 3.5% of predicted value to 72.9 +/- 7.2% (P < 0.0001) and serum ECP concentration also fell from 19.9 +/- 5.9 micrograms/L to 4.3 +/- 2.0 micrograms/L (n = 10, P < 0.01). Our data suggest both IL-3 and GM-CSF may be important in the pathogenesis of acute severe asthma.