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

Abstract

The viruses most commonly affecting the human respiratory tract include rhinoviruses, respiratory syncytial virus (RSV), influenza viruses, 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 and chemokines including IL6, IL8(CXCL8), IL1β, and tumor necrosis factor α (TNFα). A subsequent acute inflammatory response in the lungs is accompanied by an increase in the production of cytokines and chemokines − CXCR3 receptor ligands – that are key players of acute inflammatory response that induce an influx of neutrophils and T cells into the lungs.We studied the pharmacodynamic activity of the new compound XC221GI to suppress the IL6 and IL8 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 production of excessive levels 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 means of preventive anti-inflammatory therapy during a viral infection of the respiratory tract.