Ifeoluwa Oluleke Awogbindin, David Olufemi Olaleye and Ebenezer Olatunde Farombi
University of Ibadan, Nigeria
Posters & Accepted Abstracts: J Vaccines Vaccin
Implicated in influenza-associated pathology are innate defense overzealousness and unabated secretion of oxidative tissue-sensitive anti-microbial agents. We investigated the redo-immunomodulatory effect of kolaviron (KV), a natural antioxidant and antiinflammatory agent, on A/Perth/H3N2/16/09 (Pr/H3N2) escape mechanisms in mice model of influenza pneumonitis. KV (400 mg/kg) was administered orally, in different experimental set-ups, to BALB/c mice for 3/5 days prior and 2 days post infection (dpi) (intranasal; 2 or 3 LD50). Blood, lungs and spleen were collected on 2, 4, 6 and/or 8 dpi. Pr/H3N2 multiplication and expression of induced signatures of pathology in lung were immunohistochemically detected and confirmed with RT PCR. Infiltration and activation of innate immunity with resulting oxidative damage were assessed in spleen cells biochemically, immunohistochemically with RT PCR and further with flow cytometry. Disease outcome regulators were also estimated by immunohistochemistry and flow cytometry. Viral antigen hemaglutinin was sparsely detected in the lungs of KV-treated animals possibly due to reduced polymerase activity attributable to moderate recruitment of innate cells, reduced RIG-I, NOD-2, iNOS and COX-2 expressions, reduction of NO and MDA levels, diminished MPO activity and restoration of cellular redox status. KV significantly doused influenza pneumonitis and increased lung aeration. Activated signaling cascade was markedly down-regulated as hyperinduction of acute pro-inflammatory cytokines IL-1β, RANTES, MCP-1, their transcription regulators Nf-κB and STAT3 was prominently suppressed. Adaptive cellular response was evidently compromised by IAV as significant recruitment of activated and differentiated cytotoxic T-lymphocytes was accompanied with increased viral multiplication and enhanced pathology. However, KV administration resulted in moderate CD4+, CD8+ sensitivity and timely NK cells recruitment resulting in improved viral clearance and enhanced resolution of immunopathology. These data indicate that kolaviron may confer disease-dwindling properties during acute influenza infection via mechanisms involving multiple targets especially at the early stage of the infection.