Evaluation of interleukin‐1 and interleukin‐6 receptor antagonists in a murine model of acute lung injury

Author:

Meunier Émilie12,Aubin vega Mélissa12,Adam Damien12,Privé Anik1,Mohammad Nezhady Mohammad Ali3,Lahaie Isabelle3,Quiniou Christiane3,Chemtob Sylvain34,Brochiero Emmanuelle12ORCID

Affiliation:

1. Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM) Montréal Québec Canada

2. Département de Médecine Université de Montréal Montréal Québec Canada

3. Centre de recherche du Centre hospitalier Universitaire Sainte‐Justine Montréal Québec Canada

4. Département de pédiatrie Université de Montréal Montréal Québec Canada

Abstract

AbstractThe acute exudative phase of acute respiratory distress syndrome (ARDS), a severe form of respiratory failure, is characterized by alveolar damage, pulmonary oedema, and an exacerbated inflammatory response. There is no effective treatment for this condition, but based on the major contribution of inflammation, anti‐inflammatory strategies have been evaluated in animal models and clinical trials, with conflicting results. In COVID‐19 ARDS patients, interleukin (IL)‐1 and IL‐6 receptor antagonists (IL‐1Ra and IL‐6Ra, kineret and tocilizumab, respectively) have shown some efficacy. Moreover, we have previously developed novel peptides modulating IL‐1R and IL‐6R activity (rytvela and HSJ633, respectively) while preserving immune vigilance and cytoprotective pathways. We aimed to assess the efficacy of these novel IL‐1Ra and IL‐6Ra, compared to commercially available drugs (kineret, tocilizumab) during the exudative phase (day 7) of bleomycin‐induced acute lung injury (ALI) in mice. Our results first showed that none of the IL‐1Ra and IL‐6Ra compounds attenuated bleomycin‐induced weight loss and venous increase. Histological analyses and lung water content measurements also showed that these drugs did not improve lung injury scores or pulmonary oedema, after the bleomycin challenge. Finally, IL‐1Ra and IL‐6Ra failed to alleviate the inflammatory status of the mice, as indicated by cytokine levels and alveolar neutrophil infiltration. Altogether, these results indicate a lack of beneficial effects of IL‐1R and IL‐6R antagonists on key parameters of ALI in the bleomycin mouse model.

Funder

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council of Canada

Publisher

Wiley

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