Exploring a novel approach to COPD treatment: benralizumab effect in an ex vivo 3-D model.

BACKGROUND

Recent evidence supports the hypothesis that eosinophilic inflammation is a relevant component in the pathogenesis of COPD.

OBJECTIVE

The current study aimed to assess the effects of Benralizumab, on ex vivo "COPD smoke-induced" bronchial mucosa equivalents.

METHODS

Three-dimensional (3D) composite ex-vivo bronchial mucosa are used to study the mechanisms of repair, regeneration and differentiation within the epithelial-mesenchymal trophic unit (EMTU). After a one month incubation in growth medium and basal membrane extracts, epithelial cells differentiate into ciliated and mucous-producing cells, and mesenchymal cells into fibroblasts. This culture model is induced to express an inflammatory phenotype through exposure to cigarette smoke extracts. Eosinophils (Eos) are placed underneath the connective layers, whereas monocytes are activated and monocyte conditioned medium (MCM) is collected. The inflammatory cells established a cross-talk with resident cells by cytokine productions. The protocol included four experimental conditions: untreated control (K), Eos only (EO), Eos + MCM (EOMO), Eos + MCM + Benralizumab (EMB).

RESULTS

Cytokine concentrations at basal and apical side were analyzed. At basal side, IL (interleukin)-5 significantly increased after the addition of eosinophils and monocytes, and decreased after the introduction of Benralizumab to the culture (after 14 days of treatment, K group: 14.6 ± 3.2 pg/mL; EO group: 13.9 ± 4.2 pg/mL; EOMO group: 35.7 ± 5.9 pg/mL; EMB group: 14.04 ± 4 pg/mL, p < 0.005). The reduction persisted for the subsequent 14 days. IL-6 and IL-15 concentration was high in EOMO groups while EMB groups had a reduction in both interleukins concentration.

CONCLUSION

The findings described lead to speculate on a potential action of benralizumab on alternative inflammatory targets.