STEROID-RESISTANT ASTHMA - EFFECTS OF GLUCOCORTICOIDS ON INTERLEUKIN-4 AND INTERLEUKIN-5 GENE-EXPRESSION

Objective To investigate the role of interleukin-4 (IL-4) and interleu kin-5 (IL-5) in the pathogenesis of steroid-resistant (SR) asthma. Met hods Fifteen patients with SR asthma and 15 patients with steroid-sens itive (SS) asthma were selected based on their clinical responses to p rednisone therapy. The peripheral blood mononuclear cells (PBMCs) were obtained and incubated with phytohemagglutinin (PHA) in vitro for 48 h in the presence or absence of dexamethasone (10(-7) mol/L). Expressi ons of IL-4 and IL-5 mRNA in PBMCs were determined by reverse transcri ption-polymerase chain reaction (RT-PCR), and mRNA positive PBMCs for IL-4 and IL-5 were measured with in situ hybridization using digoxin-l abeled cDNA probes. Results In the absence of dexamethasone, there was no significant difference in the expressions of IL-4 and IL-5 mRNA be tween SR and SS asthmatics, and the numbers of mRNA positive cells for IL-4 and IL-5 were also similar between these two groups, however, in the presence of dexamethasone (10(-7) mol/L), expressions of IL-4 mRN A (P<0.01) and IL-5 mRNA (P<0.05) were significantly inhibited in SS a sthmatics, but not in SR asthmatics (P>0.05). The numbers of IL-4 and IL-5 mRNA positive cells decreased from 5.50 +/- 1.60 to 2.27 +/- 0.98 (P < 0.01) and from 5.03 +/- 1.29 to 1.67 +/- 0.70 ( P < 0.01), respe ctively in SS asthmatics, but in the patients with SR asthma, there wa s no significant change in the number of cells expressing mRNA for IL- 4 or IL-5. Conclusion The gene expression of IL-4 and IL-5 in SR asthm a was not inhibited by dexamethasone at the concentration of 10(-7) mo l/L. It is suggested that the relative unresponsiveness of T cells to glucocorticoids and persistent production of cytokines may be one of t he mechanisms of steroid resistance in asthma.