Anti-interleukin-5 therapy

Antibody for blocking the cytokine Interleukin-5, a glycoprotein (cytokine) consisting of 115 amino acids. The coding gene is located on the 5th chromosome. Eosinophilic granulocytes are the main source of interleukin-5. Furthermore, the cytokine is secreted by TH2 helper cells and mast cells and acts as a specific hematopoietic growth factor. The cytokine causes the transformation of thymocytes into cytotoxic T lymphocytes. Interleukin-5 is involved in the regulation of proliferation and differentiation of eosinophilic granulocytes. Overexpression of Il-5 leads to eosinophilia. IL-5 promotes differentiation of B cells and further the synthesis of IgA by plasma cells. Interleukin-5 receptors are present as high-affinity and low-affinity receptors. Besides the membrane-bound receptors (e.g. on eosinophilic granulocytes) the receptor is also present in soluble form (sIL-5R).

Anti-Interleukin-5 antibodies were originally developed for the treatment of bronchial asthma. In the meantime, further indications have been added. The following preparations can be used:

Mepolizumab (Nucala® from GSK) is first approved in December 2015 as an adjunct treatment for severe refractory eosinophilic asthma in adult patients (since summer 2018 also in children 6 years of age and older). Positive effects are also expected in eosinophilic granulomatosis with polyangiitis. The same applies to hypereosinophilic dermatitis. Furthermore, a glucocorticoid-saving effect can be expected. The preparation has received the so-called "orphan drug" status in Europe and in the USA.

Reslizumab (Cinqaero®) is approved as an additional treatment for adults with severe asthma that is not adequately controlled by a combination of inhaled high-dose corticosteroids and other drugs for the prevention of asthma.

Benralizumab: Monoclonal antibodies to the receptor "interleukin-5Ralpha" are used in patients with eosinophilic bronchial asthma.

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Anti-IL-5 therapy in atopic eczema: here too, rapid decline of eosinophils in peripheral blood, no significant clinical effect with this therapy.

Discussions are also underway on its use in chronic rhinosinusitis with nasal polyps and in hypereosinophilic syndromes.

1. Castro M et al (2016) Treatment for severe eosinophilic asthma-consistent effect of anti-interleukin-5 antibodies? Lancet 388:2059-2060.
2. Hilvering B et al (2015) Evidence for the efficacy and safety of anti-interleukin-5 treatment in the management of refractory eosinophilic asthma. Ther Adv Respir Dis 9:135-145.
3. McLeod O et al (2016) Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease. Cytokines 81:1-9.
4. Simon D et al (2007) Anti-interleukin-5 therapy for eosinophilic diseases. dermatologist 58: 122-127