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Steroid-resistant asthma: effects of glucocorticoids on interleukin-4 and interleukin-5 gene expression
1Department of Respiratory Medicine, Peking Union Medical College Hospital, Beijing 100730, China.
Objective:
To investigate the role of interleukin-4 (IL-4) and interleukin-5 (IL-5) in the pathogenesis of steroid-resistant (SR) asthma.
Methods:
Fifteen patients with SR asthma and 15 patients with steroid-sensitive (SS) asthma were selected based on their clinical responses to prednisone 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). Expressions of IL-4 and IL-5 mRNA in PBMCs were determined by reverse transcription-polymerase chain reaction (RT-PCR), and mRNA positive PBMCs for IL-4 and IL-5 were measured with in situ hybridization using digoxin-labeled cDNA probes.
Results:
In the absence of dexamethasone, there was no significant difference in the expressions of IL-4 and IL-5 mRNA between 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 mRNA (P < 0.01) and IL-5 mRNA (P < 0.05) were significantly inhibited in SS asthmatics, 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), respectively in SS asthmatics, but in the patients with SR asthma, there was 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 asthma was not inhibited by dexamethasone at the concentration of 10(-7) mol/L. It is suggested that the relative unresponsiveness of T cells to glucocorticoids and persistent production of cytokines may be one of the mechanisms of steroid resistance in asthma.