Allergen challenge primes for IL-5 mRNA production and abrogates beta-adrenergic function in peripheral blood T lymphocytes from asthmatics

Background In previous studies, we have found a dysfunctional adenylyl cycl ase (AC) system in patients with asthma after allergen provocation, which r esulted in a 40-50% decreased generation of intracellular cAMP. In addition , in activated T helper lymphocyte clones, it has been demonstrated that IF N-gamma (TH1-like cytokine) and IL-5 (TH2-like cytokine) are differentially regulated by the AC system. Therefore, we postulate that an increased IL-5 /IFN-gamma ratio as observed in asthmatics might be due to a dysfunctional AC system. Objective To assess whether a dysfunctional AC system as observed in asthma tics after allergen provocation, is responsible for an increased IL-5/IFN-g amma cytokine ratio. Methods Peripheral blood T lymphocytes of seven asthma patients were stimul ated with anti-CD3 plus anti-CD28 MoAbs in the absence and presence of isop roterenol (ISO) and prostaglandin E-2 (PGE(2)) to activate the AC system. B efore, 3 h and 24 h after allergen provocation, IFN-gamma and IL-5 mRNAs we re detected by semiquantitative RT-PCR. Results Before allergen provocation, ISO (10(-5) mol/L) significantly downr egulated IFN-gamma mRNA (P<0.03, n = 6), and showed a trend to upregulate I L-5 mRNA (P=0.138, n = 5). Three and 24 h after allergen provocation, ISO w as not longer able to modulate IFN-gamma and IL-5. In contrast with the obs ervations with ISO, PGE(2) still dose-dependently inhibited IFN-gamma mRNA, both before, 3 h and 24 hh after allergen provocation (n = 7). IL-5 mRNA, but not IFN-gamma mRNA, was significantly upregulated in anti-CD3 plus anti -CD28-activated T cells (P<0.05, n = 5) 24 h after allergen provocation, co mpared with before allergen provocation. Conclusion Twenty-four hours after allergen provocation, a significant redu ction of beta-adrenergic control on IFN-gamma and IL-5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selectiv e priming of IL-5 mRNA production.