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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.

Keywords: IFN-γ; IL-5; IL-5/IFN-γ ratio; T lymphocytes; adenylyl cyclase; allergen provocation; asthma; dysfunctional adenylyl cyclase

Document Type: Research Article

DOI: http://dx.doi.org/10.1046/j.1365-2222.1999.00552.x

Affiliations: 1: Allergology, 2: Hematology, 3: Pulmonology, Department of Internal Medicine, University of Groningen, The Netherlands

Publication date: July 1, 1999

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