Diethylcarbamazine reduces the viral titer of influenza A (H1N1)pdm09 virus and regulates IFN-β and IL-8 in infected epithelial cells

Context Influenza is a viral infection with pandemic potential that affects individuals of all ages. The immune response is key to resolving the disease; however, immune deregulation, such as cytokine storm, can cause tissue damage and death. Diethylcarbamazine (DEC), a drug with immunomodulatory effects, has demonstrated anti-inflammatory and antifibrotic properties. However, DEC’s activity in viral respiratory infections remains unknown.Objective This study aimed to analyze the effect of DEC in a model of respiratory epithelial cells infected with Influenza A (H1N1)pdm09 virus (IAV) to evaluate its action on antiviral immune effectors and viral titer.Materials and methods A549 cells were cultured, infected with IAV, and treated with DEC. Viral load was quantified at 24 h and 48 h. Subsequently, Cytokine levels (IL-1β, IL-6, IL-8, IL-10, IL-15, and RANTES) were analyzed from supernatants at both timepoints using a Bio-Plex Pro-Human Proinflammatory Cytokine kit. RNA was obtained from cells, and RT-qPCR was performed to evaluate the expression of genes encoding MYD88, NLRP3, NF-κB, IFN-β, and IFN-λ.Results and discussion Results showed that IFN-λ1 expression was consistent across all groups (p > .05). IFN-β expression increased at 24 h in DEC-treated infected groups (p < .05) but returned to baseline at 48h (p > .05). IL-8 secretion was significantly higher in the IAV + DEC20 group at 24h compared to the MOCK (p ≤ .05), but no differences were found at 48 h (p > .05). Infected cells treated with the lowest DEC dose showed a lower viral titer compared to IAV-infected (p ≤ .05).Conclusion DEC maintained IFN-λ1 expression, regulated levels of IFN-β and IL-8, and reduced viral load in IAV-infected epithelial cells.