Recent Developments in Targeting Eosinophil Accumulation as a Novel Therapeutic Approach for Asthma

Abstract

Current therapies for asthma are aimed at controlling disease symptoms and for the majority of patients inhaled glucocorticoid anti-inflammatory therapy is both effective and well-tolerated. However, concerns remain about the adverse effects of glucocorticoids while a subset of asthmatic patients remains symptomatic despite optimal treatment thereby creating a clear unmet medical need. There is considerable evidence that implicates eosinophils as important effector cells and immunomodulators in the inflammation characteristic of asthma. Numerous in vitro and animal studies have demonstrated essential roles for cell adhesion molecules in eosinophil adhesion and transendothelial migration including the selectins, ICAM-1, VCAM-1 together with many of the μ1 and μ2 integrins. A large body of evidence has also implicated several cytokines and chemokines in the selective recruitment of eosinophils to sites of asthmatic inflammation. Biopharmaceutical approaches have been used to identify inhibitory molecules that target key elements in the processes controlling eosinophil accumulation in asthma. This review will summarise the problems and successes regarding recent developments in therapeutic strategies aimed at reducing eosinophil-mediated inflammation in the asthmatic lung.

Fluvastatin and lovastatin inhibit granulocyte macrophage–colony stimulating factor‐stimulated human eosinophil adhesion to inter‐cellular adhesion molecule‐1 under flow conditions

“…The preferential accumulation of eosinophils in the asthmatic lung suggests the existence of pathways for their selective accumulation. This involves enhanced eosinophil production and release from the bone marrow followed by a combination of selective adhesion to the post‐capillary vascular endothelium and trans‐endothelial migration (TEM) into the surrounding tissues [6]. There is general agreement that the introduction of flow conditions to in vitro models of leucocyte adhesion is crucial to the generation of data relevant to the in vivo situation [7].…”

Emerging drugs for asthma

“…Numerous animal studies have demonstrated essential roles for these cell adhesion molecules in the lung inflammation underlying asthma pathogenesis, including L-selectin, P-selectin, and E-selectin, ICAM-1 and VCAM-1, together with many of the α 1 and α 2 integrins [55] . These therefore represent potentially important therapeutic targets; these families of adhesion molecules have been under intense investigation by the pharmaceutical industry for the development of novel therapeutics.…”