Get access
Advertisement

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

Authors


Kauffman Division of Allergology, Department of Internal Medicine, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.

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.

Get access to the full text of this article

Ancillary