IL-5: biology and potential therapeutic applications

Abstract

IL-5 is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of Th-2 cells leads to the production of IL-5. The pro-eosinophilic 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) that are expressed on the eosinophil cell membrane. Intracellular signalling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45 kDa glycoprotein consisting of two identical polypeptide chains. The 5'-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. Anti-IL-5 reagents have the potential to suppress IL-5 activity without the side effects of glucocorticoids. Studies using monoclonal antibodies (mAbs) against IL-5 have established the feasibility of suppressing eosinophilic inflammation by specifically blocking IL-5 activity. Studies with antisense IL-5 are beginning to provide the basis for non-glucocorticoid, sequence-specific oligonucleotide inhibitors of IL-5. Research has begun on the development of mAbs and antisense oligonucleotide inhibitors of IL-5 that can be inhaled and applied topically.

Crucial Role of IL-4/STAT6 in T Cell-Mediated Hepatitis: Up-Regulating Eotaxins and IL-5 and Recruiting Leukocytes

“…The critical effect of IL-5 in liver injury and eosinophil infiltration in Con A-mediated hepatitis has been previously demonstrated in IL-5-deficient mice and by depletion of IL-5 with neutralizing IL-5 Abs (30). It is believed that IL-5 is responsible for eosinophil precursor maturation, proliferation, and trafficking within tissues through CC chemokine receptors (CCR3) (37)(38)(39). Although the physiological significance of eotaxins has been extensively investigated (40 -44), its role in liver disease remains poorly characterized.…”

Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production

“…Induction of IL-5 could result in the development of eosinophils observed in the periphery and marrow of the hIL-17E transgenic mice, because IL-5 is a primary cytokine responsible for eosinophilopoiesis. [39][40][41][42] Both IL-5 and the chemokine eotaxin have been implicated in the production and recruitment of eosinophils to sites of allergic or asthmatic reactions, particularly in the lungs. 42,43 With increased IL-17Rh1 expression on cells in the transgenic lungs, IL-17E may have a direct stimulatory effect on these cells resulting in inflammation, as well as in inducing IL-5 and eotaxin production to recruit eosinophils to the lungs.…”

Recent advances in the pathological understanding of eosinophilic esophagitis

“…IL-5 is a glycoprotein with a molecular weight of 40–50 kDa 36, 37 . IL-5 is similar to other hematopoietic cytokines such as IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) 36, 37 .…”

“…IL-5 is a glycoprotein with a molecular weight of 40–50 kDa 36, 37 . IL-5 is similar to other hematopoietic cytokines such as IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) 36, 37 . IL-5 exerts its effects by binding to its receptor IL-5R, which is composed of 2 chains: the IL-5Rα subunit, which specifically binds only IL-5 and IL-5Rβ common (βc) signaling subunit, which can also recognize IL-3 and GM-CSF 37, 38 Cells that can produce IL-5 are eosinophils, basophils, CD34+ progenitor cells, Th2 cells, mast cells, iNKT cells and non-B/non-T cells, which most have been implicated in the pathogenesis of EoE.…”