Kolaviron Improves Morbidity and Suppresses Mortality by Mitigating Oxido-Inflammation in BALB/c Mice Infected with Influenza Virus

Abstract

Influenza A viruses (IAV) induce cytokine storm and host's intracellular redox imbalance to ensure continuous replication and survival, leading to severe immunopathology and death.

Mechanistic perspective of the oxido‐immunopathologic resolution property of kolaviron in mice influenza pneumonitis

“…This may be directly associated with its established immunomodulatory and antioxidative roles as well as its suppressing effect on NO production. This is consistent with earlier suggestions and observations necessary for immunopathologic resolution in influenza‐induced pneumonitis . Moreover, we observed that innate cells accumulation and activation correlated well with total thiol levels in both challenged and treated groups.…”

“…Using a 14‐day mouse model of acute influenza infection, we had earlier demonstrated that kolaviron (400 mg/kg) pre‐treatment, at various time points ranging from 1 h to 3 days, to H3N2 influenza virus‐challenged mice significantly enhanced survival (up to 80% protective index) and protected the mice despite detection of viral particles in the lungs of the treated animals . Again, in this 6‐day study, kolaviron conferred significant protection with paltry detectable viral particles in the pulmonary tissue of the treated mice.…”

“…Reports abound that this subsequently results in taxis‐driven influx, accumulation and activation of innate inflammatory cells, neutrophils, monocytes, dendritic cells and macrophages, which if finely orchestrated, may lead to viral clearance and disease resolution, or when excessively unleashed, result in severe immunopathological damage, illness and fatality . We reported excessive pulmonary activation of neutrophils and macrophages when mice were infected with Pr/H3N2 . Together, these two constituents of innate immunity have been directly implicated in lung pathology as they occlude pulmonary parenchyma thus blocking its function.…”

“…Mice were given kolaviron orally at a dosage of 400 mg/kg/day for a day or 3 days precisely 1 h before they were intranasally challenged with influenza A/H3N2/Perth/16/09 virus. Given that better results were observed with ‘1 h’ and ‘3 days’ pre‐treatment groups in our previously published work and the fact that concurrent kolaviron administration with an ongoing infection was postulated to confer additional benefits, the ‘3 h prior’ dosage in the published work was substituted with a 3‐day pre‐treatment regimen which continued for 2 days post challenge in this study. A sublethal dose of the virus that caused mortality onset at day 8 p.i.…”

“…We have previously demonstrated in a preliminary report via 14‐day observational/survival studies that kolaviron may delay mortality onset, improve morbidity and ameliorate disease severity/pathology. While kolaviron may not dictate absolute viral clearance, it was reported in the study that kolaviron at single and multiple doses improved lungs aeration, reduced lung consolidation and pulmonary cellular infiltration, and attenuated myeloperoxidase activity and nitric oxide production . In this expanded study, we evaluated mechanistically the immunomodulatory effect of kolaviron on some specific oxido‐inflammatory mediators implicated in the immunopathogenesis of influenza virus in BALB/c mice challenged with influenza A/Perth/H3N2/16/09 (Pr/H3N2) virus.…”