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The Effect of P38 MAP Kinase Inhibition in a Mouse Model of Influenza

Growcott, Ellena and Bamba, Douty and Galarneau, Jean-Rene and Leonard, Vincent and Schul, Wouter and Stein, Daniel and Osborne, Colin (2018) The Effect of P38 MAP Kinase Inhibition in a Mouse Model of Influenza. Journal of Medical Microbiology. ISSN 0022-26151473-5644

Abstract

Influenza viruses are a common cause of human respiratory infections, resulting in epidemics of high morbidity and mortality. Previous work has suggested p38 MAPK inhibition could reduce viral replication and this was examined in vitro and in a murine influenza model. In vitro, the antiviral effect of p38 MAPK inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells; in vivo, female BALB/c mice were infected intranasally with 150 pfu of influenza A/Puerto Rico/8/34 and, treated with a closely related p38 MAPK inhibitor BCT197, dexamethasone or oseltamivir starting 24 hours post infection. Body weight, bronchoalveolar lavage cells, cytokines, total protein and lactate dehydrogenase as well as serum cytokines were measured; a subset of animals was evaluated histopathologically. Contrary to previous reports, inhibition of p38MAP kinase did not result in an effect on influenza replication. There was, however, improved weight loss, survival and lack of impaired viral control (when compared to untreated animals) at BCT197 doses relevant to those being used in clinical trials of acute exacerbations of COPD. As the use of inhibitors of innate inflammatory pathways may raise the concern of negative effects on infection regulation, this is encouraging.

Item Type: Article
Date Deposited: 16 Feb 2018 00:45
Last Modified: 16 Feb 2018 00:45
URI: https://oak.novartis.com/id/eprint/31291

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