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

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2017-03, Vol.125 (3), p.184-196
• Main Authors: Awogbindin, Ifeoluwa O., Olaleye, David O., Farombi, Ebenezer O.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Cytokines; Disease Models, Animal; Flavonoids - pharmacology; Immunohistochemistry; Infections; Inflammation - pathology; Influenza; influenza pneumonitis; Kolaviron; Lung - drug effects; Lung - pathology; MCP‐1; Mice; Mice, Inbred BALB C; NF‐κB; Nitric oxide; Orthomyxoviridae Infections - pathology; Oxidative Stress - drug effects; oxido‐immunopathology; Pneumonia, Viral - pathology; RANTES
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/apm.12640

Implicated in influenza‐associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue‐sensitive antimicrobial agents. At different time points, mice were pre‐treated with kolaviron (400 mg/kg), a natural antioxidant and anti‐inflammatory agent, and subsequently challenged with 2 LD50 influenza A/H3N2/Perth/16/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo‐inflammatory imbalance, cytokine storm indices and T helper 1 host response. Previously kolaviron was reported to delay mortality onset, improve morbidity and attenuate myeloperoxidase activity and nitric oxide production with minimal impact on viral clearance. This study additionally confirmed nitric oxide, but not hydrogen peroxide, as the major culprit implicated in influenza virus‐induced oxido‐pathology. Systemic effect of the sustained inflammation and nitrosative stress was more prominent in the spleen and lung than in the liver of mice infected with A/H3N2/Perth/16/09. Influential to immunopathology was heightened pulmonary expression of IL‐1β, RANTES, IL‐10, MCP‐1, NF‐κB, iNOS and COX‐2. However, kolaviron combated the influenza‐established nitrative stress, reversed the elicited cytokine storm and restored the oxidized environment to a reductive milieu. Our data also suggest that kolaviron administration early in infection may foster CD4+ response. These data indicate that kolaviron may confer disease‐dwindling properties during acute influenza infection via a system‐wide protective approach involving multiple targets especially at the early stage of the infection.