Increased uric acid levels in bronchoalveolar lavage fluid of mice infected with H1N1 influenza

Rationale: Lower respiratory tract infections with influenza are associated with severe inflammatory responses, which may result in ALI/ARDS. Tissue injury results in the release of damage-associated molecular patterns (DAMPs), such as uric acid and ATP, leading to NLRP3/inflammasome activation and IL-1β release. Hypothesis: We hypothesized that influenza-induced lung injury is associated with the release of DAMPs into the airway lumen. Methods: C57Bl/6 mice were inoculated with 10TCID50 influenza A/PR/8/34 (H1N1) and sacrificed 4, 8 and 14 days later to collect BALF to determine uric acid, extracellular ATP and markers of inflammation and lung injury. Non-infected mice were sacrificed on day 0 for control measurements. Results: Influenza virus infection resulted in bodyweight loss between day 6 and day 11 (p<0.05) and returned to normal values on day 14 after infection. Uric acid levels in BALF were significantly increased on day 8 after viral infection (52.7-115.9 μM vs 12.2-25.8 μM in control mice, 95% CI, p<0.01), while ATP was undetectable. Uric acid in BALF was associated with increased levels of inflammatory markers (IL-6, KC and IFN-γ) as well as markers of lung injury (sRAGE and total protein in BALF). However, increased IL-1β levels, indicative for inflammasome activation, were only observed on day 4 after influenza infection (p<0.01). Conclusion: Uric acid in BALF is increased during influenza infection and associates with biomarkers of inflammation and lung injury, but not with markers of inflammasome activation. Whether uric acid fails to activate NLRP3/inflammasome or that IL-1β is scavenged by IL-1 receptor antagonist during influenza infection remains to be determined.