Dimethyl Sulfoxide Modulates T Cell-Mediated Immunity to Attenuate Influenza A Virus Infection.

Purpose: Influenza A virus (IAV) remains a major threat because vaccines provide limited cross-protection and antiviral resistance is rising. Dimethyl sulfoxide (DMSO) is immunomodulatory, but its effect on IAV has not been tested in vivo. We evaluated its efficacy and mechanism in a murine H1N1 model. Methods: Male C57BL/6 mice were intranasally challenged with an LD50 of A/Puerto Rico/8/1934 (H1N1) and given daily subcutaneous DMSO (0.22 g/kg/day) or phosphate-buffered saline (PBS) on days 1-7. Survival was monitored for 21 days; lung and bronchoalveolar lavage fluid (BALF) were collected on day 8. Lung histology (hematoxylin and eosin), BALF cytokines (sandwich ELISA), lung and splenic IFN-γ-producing CD4+ and CD8+ T cells (flow cytometry), and whole-lung RNA sequencing (differential expression, KEGG enrichment) were assessed. BALF viral burden was measured by neuraminidase activity assay and TCID50. In vitro, splenic CD8+ T cells exposed to 0%, 0.5%, or 1.0% DMSO were immunoblotted for lymphocyte-activation gene 3 (LAG3). Results: DMSO significantly improved 21-day survival and attenuated alveolar inflammatory infiltration. Day-8 BALF viral titers were significantly lower with DMSO (mean 2.2×10 Conclusion: DMSO is associated with attenuated IAV severity, a lower day-8 airway viral burden, and a localized expansion of IFN-γ-producing CD8+ T cells, without a concomitant rise in the pro-inflammatory cytokines TNF-α, IL-6, or IL-1β. These associations are correlative and support further investigation of DMSO as a host-directed adjunct for influenza.