Interleukin-5: A Proeosinophil Cytokine Mediator of Inflammation in Asthma and a Target for Antisense Therapy

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Abstract:

Interleukin-5 (IL-5) is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of TH2 cells leads to the production of IL-5. The proeosinophilic effects of IL-5 include 1) enhanced replication and differentiation of eosinophilic myelocytes; 2) enhanced degranulation of eosinophils; 3) prolonged survival time of eosinophils; and 4) enhanced adhesion of eosinophils. The effects of IL-5 are mediated via the interaction of IL-5 with receptors (Il-5R) expressed on the eosinophil cell membrane. Intracellular signaling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45kD glycoprotein that consists of two identical polypeptide chains. The 5′-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. A 16-mer deoxyoligonucleotide, antisense to IL-5 mRNA and with two phosphorothioate modifications, produced, at 20 micromolar concentration, complete inhibition of IL-5 secretion by human peripheral blood mononuclear cells. The targeted 16-mer sequence of the IL-5 mRNA did not display complete homology with any other known human gene sequences. These results suggest that the 16-mer phosphorothioate antisense IL-5 provides the basis for a non-glucocorticoid, sequence-specific inhibitor of IL-5.

Document Type: Research Article

DOI: http://dx.doi.org/10.2500/108854198778557782

Publication date: September 1, 1998

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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