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Interleukin-5

Immunological Functions and Therapeutic Potential of a Putative Antagonist

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Summary

Interleukin-5 (IL-5) is an interdigitating homodimeric glycoprotein and features the 4-α-helical-bundle motif which is conserved among several haemopoietic cytokines. It is a potent cytokine which induces proliferation and differentiation of activated B cells and induces eosinophil production and activation. IL-5 acts on target cells by binding to its specific receptor. The IL-5 receptor consists of a unique α chain and a β (βc) chain that is shared with the receptors for interleukin-3 and granulocyte-macrophage colony-stimulating factor. The βc chain is indispensable for signal transduction. Both subunits contain motifs conserved among the superfamily of cytokine receptors.

Stimulation of cells by IL-5 induces rapid tyrosine phosphorylation of various cellular proteins, including the βc chain, and activates the Bruton tyrosine (Btk) and JAK2 kinases. The cytoplasmic domain of the βc chain and the membrane-proximal proline-rich sequence of the cytoplasmic domain of the α chain are both essential for the IL-5-induced proliferative response, for expression of nuclear proto-oncogenes and for activation of the Btk and JAK2 kinases. B cells from X-linked immunodeficient (XID) mice, which have an abnormality of Btk and lack functionally mature B cells, including CD5+ B cells, show impaired responsiveness to IL-5, whereas eosinophils from these animals respond normally.

In several pathophysiological conditions, increases in serum and tissue levels of IL-5 and eosinophil numbers have been described. Of clinical relevance is a role for IL-5 in hypereosinophilic syndromes and atopic disease. An animal model of local allergen (airways) sensitisation was employed to study the effects of anti-IL-5 monoclonal antibody on infiltration of eosinophils into inflammatory regions and the development of the antigen-induced late-phase asthmatic response and subsequent bronchial responsiveness. Treatment with the anti-IL-5 antibody decreased the enhanced bronchial responsiveness to acetylcholine induced by allergen sensitisation via the airways.

These diverse biological consequences of IL-5 provide the basis for elucidating the functional structure of IL-5 and its receptor complex, as well as the mechanisms of IL-5 signal transduction. Furthermore, clinical studies provide insight into the role of IL-5 in health and disease and provide a strong impetus for investigating means of modulating the effects of IL-5. In concert with advances in understanding the biology of other cytokines and growth factors, entirely new approaches to patient care should emerge in the near future.

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  1. Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108, Japan

    Kiyoshi Takatsu

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Takatsu, K. Interleukin-5. BioDrugs 8, 33–45 (1997). https://doi.org/10.2165/00063030-199708010-00005

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