In vitro and in vivo pharmacodynamic activity of the new compound XC221GI in models of the viral inflammation of the respiratory tract

Abstract

The viruses that most commonly affect human respiratory tract include rhinoviruses, respiratory syncytial viruses (RSVs), influenza, and coronaviruses (CoVs). The virus infection of the epithelial cells of the respiratory tract triggers an inflammation accompanied by the release of pro-inflammatory cytokines/chemokines including IL6, IL8 (CXCL8), IL1β, and tumor necrosis factor α (TNFα). The transition of the infection to the acute inflammatory phase in the lungs is accompanied by an increase in the production of cytokines, an influx of neutrophils and T cells into the lungs, and the induction of chemokines – CXCR3 receptor ligands – the main participants of generalized inflammation. We studied the pharmacodynamic activity of the new compound XC221GI and its effect on release of the IL6 and IL8 in the course of an experimental RSV infection in vitro in human lung carcinoma cells A549 and in vivo in the lungs of cotton rats. We also studied the effect of XC221GI on the production of the chemokines CXCL10, CXCL9, and CXCL11 in mouse bronchoalveolar lavage as well as on the influx of neutrophils into the mouse lungs after the intranasal administration of interferon γ (IFNγ). The obtained results demonstrate the anti-inflammatory activity of XC221GI, which suppresses the excessive production of the key inflammatory markers IL6, IL8, CXCL10, CXCL9, and CXCL11 as well as the influx of neutrophils into the lungs thereby reducing lung pathology. These data confirm the effectiveness of XC221GI as a medicine for preventive anti-inflammatory therapy during a viral infection of the respiratory tract.