IL-5 (Interleukin 5) is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, interleukin 5 is a very selective cytokine as a result of the restricted expression of the interleukin 5 receptor on eosinophils and basophils.
Herein, we will mainly discuss IL-5 discovery & structure, IL-5 receptor, IL-5 biological role and anti IL-5 (interleukin 5) & IL-5RA therapy.
IL-5 (interleukin 5) was described for the first time as an eosinophil and B-cell growth factor in 1987. IL-5 is encoded by a single 4-exon gene found on murine chromosome II and human chromosome 5 that is clustered near the genes for IL-3, IL-4 and GM-CSF. IL-5 is a 115-amino acid (in human, 133 in the mouse) -long TH2 cytokine. The structure of IL-5 is characterized by 4 helices with antiparallel conformation.
The specific IL-5 receptor (IL-5R) consists of the IL-5 receptor α subunit (IL-5RA) and the common receptor β subunit (βc). The βc is indispensable for signal transduction, which is shared with the receptors for interleukin-3 and GM-CSF. Both subunits contain motifs conserved among the superfamily of cytokine receptors. IL-5 binding to IL-5R on target cells induces rapid tyrosine phosphorylation and activation of various cellular proteins, including JAK1/JAK2 and STAT1/STAT5.
IL-5 (interleukin 5) is produced by type 2 T helper cells (Th2), mast cells, and eosinophils, and non-hematopoietic cells. IL-5 has pleiotropic actions, from enhancing the homeostatic proliferation and survival of B-1 cells through noncognate stimulation and driving the differentiation of B-1 and B-2 cells into terminally differentiated plasma cells to augmenting the survival and activation of eosinophils.
Thus, IL-5 links natural and adaptive immunity specific to the epitopes of natural ligands and exogenous antigens leading to the inducion of Ig-producing cells, regulating chronic inflammation and controlling disease. The potential roles of IL-5 in immune responses, allergy and autoimmunity make it attractive candidate for use in the clinical setting.
Anti IL-5 (interleukin 5) & IL-5RA therapy has been shown to be effective in patients with severe eosinophilic asthma. Two different anti-IL-5 monoclonal antibodies (mepolizumab and reslizumab) bind to distinct epitopes of IL-5 interfering with its binding to IL-5R expressed on eosinophil membrane.
Mepolizumab, a humanized monoclonal antibody, has been approved in 2015 by the US FDA and European Medicine Agency as an add-on treatment for adult patients with severe eosinophilic asthma.
Reslizumab, another humanized anti-IL-5 monoclonal antibody, has been shown to be effective in patients with asthma. Based on these clinical studies, reslizumab has been recently recommended by FDA for approval for treatment of adult patients with severe eosinophilic asthma.
Benralizumab, a humanized monoclonal antibody, is directly against the IL-5RA (interleukin 5 receptor alpha subunit) present on eosinophils and basophils. Benralizumab is still under clinical phase III for additional studies are needed to assess the disease-modifying effects.
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