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The effect of glucocorticoid on T cell activation, interleukin‐4 and interleukin‐5 mRNA expression in patients with steroid‐resistant asthma
Author(s) -
Sun Yongchang,
Luo Weici
Publication year - 1999
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1046/j.1440-1843.1999.00217.x
Subject(s) - dexamethasone , oxymatrine , medicine , glucocorticoid , prednisone , endocrinology , asthma , peripheral blood mononuclear cell , interleukin , interleukin 2 , interleukin 4 , lymphocyte , in vitro , immunology , cytokine , pharmacology , biology , biochemistry
To investigate the mechanisms of steroid‐resistant (SR) asthma, we studied: (i) serum levels of sIL‐2R before and after oral prednisone therapy; (ii) the inhibitory effects of dexamethasone and oxymatrine on PHA‐induced lymphocyte proliferation; and (iii) the effect of dexamethasone (10 –7 mol/L) on interleukin (IL)‐4 production and IL‐4 and ‐5 mRNA expression in PBMC cultures. Fifteen patients with SR asthma were selected, and 15 patients with steroid‐sensitive (SS) asthma served as controls. Levels of sIL‐2R and IL‐4 were measured using an ELISA kit. Interleukin‐4 and ‐5 mRNA were measured with semi‐quantitative reverse transcriptase–polymerase chain reaction. The results showed that there was no difference in the baseline serum levels of sIL‐2R between SR and SS asthmatics, but after prednisone (20 mg/d, 7 days) therapy, levels of sIL‐2R were significantly decreased in SS asthmatics ( P < 0.001), but not in SR asthmatics. The inhibitory effects of dexamethasone on proliferation of lymphocytes from SR asthmatics were significantly less than those from SS asthmatics ( P < 0.002), but oxymatrine inhibited cell proliferation to a similar degree between these two groups. Dexamethasone inhibited in vitro production of IL‐4 by lymphocytes from both SR and SS asthmatics, but the degree of inhibition was higher in SS asthmatics ( P < 0.001). There was no difference in expressions of IL‐4 and ‐5 mRNA between SR and SS asthmatics, but after dexamethasone treatment, mRNA expressions were significantly decreased in SS asthmatics but not in SR asthmatics. The results indicate that persistent T cell activation due to reduced responsiveness of the cells to glucocorticoids may be the immunological feature of asthma. T cells from SR asthmatics remained responsive to other agents with immunosuppressive effect, which suggests that these agents may be of therapeutic benefit in the management of SR asthma.