Interleukin-5 and its receptor: a drug target for eosinophilia associated with chronic allergic disease

Abstract

A characteristic feature of chronic allergic diseases such as asthma is the increase in eosinophil numbers in the inflamed tissue. In light of its specificity for the development of eosinophils, interleukin-5 (IL-5) is considered the most important cytokine involved in the regulation of eosinophilia. Hence, an antagonist for IL-5 activity is a new target for drug discovery programs. We have examined the opportunity for both a random and a rational approach for the identification of such an antagonist. The elucidation of the structure of IL-5 and the initial structure/function analysis of the ligand/receptor complex constitute a first step towards the design of antagonistic compounds. The identification of a small compound by random screening able to inhibit the IL-5/IL-5 receptor interaction indicated an important domain in the receptor. We examine here protein-based IL-5 antagonists, such as IL-5-muteins, soluble IL-5 receptor constructs, and monoclonal antibodies, for their potential as IL-5/IL-5 receptor antagonists, and the use of a murine model of eosinophil airway inflammation for their evaluation.

Myelodysplastic/myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24): first description of a case

“…This might at least partly explain the dysplastic megakaryopoiesis and the leftward-shifted myelopoiesis in our patient. Even more, IL-5 is know n to be imp ortan t for eosin ophil opoiesis [9], which might also explain the marked peripheral and bone marrow eosinophilia. Interestingly, eosinophilia is seen in other hematologic malignancies associated with aberrations of chrom osome 8 [10,11], especi ally in the 8p11 myelo proliferative syndro me [12].…”

New anti-asthma therapies: suppression of the effect of interleukin (IL)‐4 and IL‐5

“…Although this has resulted in the identification of a number of promising molecules [76], some of them have proven to be too toxic for therapeutic applications or have been shown to also block IL-3 and GM-CSF mediated effects, again eliminating them as potential therapeutic agents [77,78]. These various points illustrate the difficulty in properly antagonizing IL-5 receptor activation.…”

Efficacy and Safety of Allergen-Specific Immunotherapy in Rhinitis, Rhinoconjunctivitis, and Bee/Wasp Venom Allergies

“…Other new approaches to immunotherapy include use of recombinant technology to produce pure, reproducible, easily standardized molecules from the antigens to which a particular individual is sensitive and the development of bioengineered muteins [5,6,21]. These muteins are modified allergen molecules that retain the ability to stimulate Th1 T-cell responses without reacting with specific IgE antibodies.…”