Interleukin‐5 as a pleiotropic cytokine orchestrating airway type 2 inflammation: Effects on and beyond eosinophils
Kathleen M. Buchheit, Dominick Shaw, Geoffrey Chupp, Lauri Lehtimäki, Enrico Heffler, Tricia Finney‐Hayward, James Zangrilli, Justin Kwiatek, Salman Siddiqui, Florence Roufosse, Andrew Thamboo, Nicholas P. West, Anna Vichiendilokkul, Peter W. Hellings, Anju T. Peters, Peter Howarth
Abstract
Interleukin (IL)-5 is the key cytokine in the maturation, activation, proliferation, migration and survival of eosinophils, which are key effector cells in many upper and lower airway diseases. Through its effects on eosinophils, IL-5 indirectly contributes to various pathophysiological processes including tissue damage, repair and remodelling. Understanding the importance of IL-5 in eosinophil-associated diseases led to the development of anti-IL-5 therapies, which provide clinical benefits across a range of conditions. However, recent evidence suggests that eosinophil-depletion alone may not account for all of the therapeutic effects of anti-IL-5 therapy and that IL-5 may also contribute to disease independently of its effects on eosinophils. Indeed, evidence from ex vivo studies and targeted therapy in vivo demonstrates that IL-5 and its inhibition affects a much broader range of cells beyond eosinophils, including epithelial cells, plasma cells, mast cells, basophils, neutrophils, type 2 innate lymphoid cells, T regulatory cells and fibroblasts. This review will provide an update on the evidence supporting the breadth of IL-5 biology relevant to disease pathogenesis beyond eosinophil-associated inflammation, where there is a need for additional insight, and the clinical implications of a more central role of IL-5 in type 2 inflammation.