title: Allergen challenge primes for IL-5 mRNA production and abrogates beta-adrenergic function in peripheral blood T lymphocytes from asthmatics.
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-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 asthmatics after allergen provocation, is responsible for an increased IL-5/IFN-gamma 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-gamma and IL-5 mRNAs were detected by semiquantitative RT-PCR.
  
  
  RESULTS
  Before allergen provocation, ISO (10-5 mol/L) significantly downregulated IFN-gamma 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-gamma and IL-5. In contrast with the observations with ISO, PGE2 still dose-dependently inhibited IFN-gamma mRNA, both before, 3 h and 24 h 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, compared with before allergen provocation.
  
  
  CONCLUSIONS
  Twenty-four hours after allergen provocation, a significant reduction of beta-adrenergic control on IFN-gamma and IL-5 mRNA expression was observed in peripheral blood T lymphocytes, which coincides with a selective priming of IL-5 mRNA production.
authors.affiliation: Allergology; Hematology; Pulmonology, Department of Internal Medicine, University of Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Borger
authors.forename: G J
authors.initials: GJ
authors.lastname: Jonker
authors.forename: E
authors.initials: E
authors.lastname: Vellenga
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.forename: J G
authors.initials: JG
authors.lastname: De Monchy
authors.forename: H F
authors.initials: HF
authors.lastname: Kauffman
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000911:Antibodies, Monoclonal; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D017931:DNA Primers / Q000737:chemistry; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics*; D007545:Isoproterenol / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D015848:Interleukin-5; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D007371:Interferon-gamma; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D007545:Isoproterenol