First-generation antihistamines diphenhydramine and chlorpheniramine reverse cytokine-afforded eosinophil survival by enhancing apoptosis

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Abstract:

Antihistamines or histamine H1-receptor antagonists are commonly used to treat a variety of allergic symptoms. Eosinophils are considered to play an essential role in the pathogenesis of allergy. Reduced eosinophil apoptosis is thought to be an important element in the formation of eosinophilia in allergic conditions such as allergic rhinitis, atopic eczema, and asthma. The aim of this study was to investigate the effects of two first-generation antihistamines diphenhydramine and chlorpheniramine on constitutive eosinophil apoptosis and on interleukin (IL)-5–afforded eosinophil survival. The role of c-Jun N-terminal kinase (JNK) in mediating the effects of antihistamines on eosinophil apoptosis was evaluated also. Apoptosis of isolated human eosinophils was assessed by measuring the relative DNA content of propidium iodide–stained cells and confirmed by morphological analysis. The activity of JNK was measured by Western blotting. Antihistamines were found to reverse the survival-prolonging effect of IL-5 in eosinophils by enhancing apoptosis. JNK was found to be activated slowly during diphenhydramine-induced eosinophil apoptosis. An inhibitor peptide specific for JNK, L-JNKI1 (JNK peptide inhibitor 1, L-stereoisomer), inhibited diphenhydramine-mediated eosinophil apoptosis. Our results suggest that first-generation antihistamines diphenhydramine and chlorpheniramine reverse IL-5–afforded eosinophil survival and that the enhanced apoptosis by antihistamines is mediated through activation of JNK. Thus, reversal of IL-5–afforded eosinophil survival may contribute to the antiallergic actions of diphenhydramine and chlorpheniramine.

Keywords: ANTIHISTAMINES; APOPTOSIS; EOSINOPHILS; IL-5; JNK

Document Type: Research Article

DOI: http://dx.doi.org/10.2500/aap.2007.28.2961

Affiliations: 1: The Immunopharmacology Research Group, Medical School, Tampere University Hospital, Tampere, Finland; Research Unit, Tampere University Hospital, Tampere, Finland 2: Department of Pharmacology and Therapeutics, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada 3: Research Unit, Tampere University Hospital, Tampere, Finland; Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland

Publication date: January 1, 2007

More about this publication?
  • Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.

    The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma.

    Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.

    Articles marked "F" offer free full text for personal noncommercial use only.

    The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
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