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

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Abstract
Background: In previous studies, we have found a dysfunctional adenylyl cyclase (AC) system in patients with asthma after allergen provocation, which resulted in a 40–50% decreased generation of intracellular cAMP. In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN‐γ (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‐γ ratio as observed in asthmatics might be due to a dysfunctional AC system.Objective: To assess whether a dysfunctional AC system as observed in asthmatics after allergen provocation, is responsible for an increased IL‐5/IFN‐γ cytokine ratio.Methods: Peripheral blood T lymphocytes of seven asthma patients were stimulated with anti‐CD3 plus anti‐CD28 MoAbs in the absence and presence of isoproterenol (ISO) and prostaglandin E2 (PGE2) to activate the AC system. Before, 3 h and 24 h after allergen provocation, IFN‐γ and IL‐5 mRNAs were detected by semiquantitative RT‐PCR.Results: Before allergen provocation, ISO (10−5 mol/L) significantly downregulated IFN‐γ mRNA (P < 0.03, n = 6), and showed a trend to upregulate IL‐5 mRNA (P = 0.138, n = 5). Three and 24 h after allergen provocation, ISO was not longer able to modulate IFN‐γ and IL‐5. In contrast with the observations with ISO, PGE2 still dose‐dependently inhibited IFN‐γ mRNA, both before, 3 h and 24 h after allergen provocation (n = 7). IL‐5 mRNA, but not IFN‐γ mRNA, was significantly upregulated in anti‐CD3 plus anti‐CD28‐activated T cells (P < 0.05, n = 5) 24 h after allergen provocation, compared with before allergen provocation.Conclusion: Twenty‐four hours after allergen provocation, a significant reduction of β‐adrenergic control on IFN‐γ and IL‐5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selective priming of IL‐5 mRNA production.

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