Does Eosinophil Depletion in Gastroenteric Diseases Associated With the Hypereosinophilic Syndrome Teach Us Whether Normal Humans Need Eosinophils in 2022?

Benralizumab ablates eosinophils by marking them for antibody-dependent cell-mediated cytotoxic destruction.7 In contrast to the IL-5–neutralizing antibodies, benralizumab appears to markedly, essentially totally, deplete eosinophils from treated patients with asthma, as judged by eosinopenia,8,9 sputum analyses,9 bronchial biopsies,9 and bone marrow aspirates.9 Presently, benralizumab is approved for treatment of severe asthma. Because of the potent ability that benralizumab has to reduce eosinophils in blood and tissues, Kuang et al10 conducted a phase 2 clinical study of its effectiveness in the hypereosinophilic syndromes (HESs). [...]patients were benefited both symptomatically and on endoscopic inspection but not uniformly. [...]the relatively short duration of the study precludes judgment of the potential for long-term benefit or long-term detriment from benralizumab treatment. [...]measurements of other likely interacting factors, including mast cells and cytokines, were not informative, with the possible exception of increased serum IL-4 levels; this argues that medications to block IL-4 might have enhanced value, and several studies have supported the benefit of dupilumab in eosinophilic esophagitis.12 Lastly and importantly, despite the complete ablation of eosinophils from the gastrointestinal tract, no pattern of adverse effects occurred.