Background Acute lung injury (ALI) is a clinical syndrome characterized by acute hypoxic respiratory failure and massive pulmonary infiltrate. Strong acid-containing gastric juice stimulates pulmonary epithelial cells and raises airway permeability, and this suggests that acid can be a trigger of ALI. However, little is known about underlying mechanism of neutrophilic infiltration in response to gastric acid aspiration. Uric acid, one of damage-associated molecular patterns (DAMPs), is released from injured cells and mediates neutrophilic response, and it possibly triggers acute response in ALI.

Objectives To test whether uric acid mediates murine acid-induced acute lung inflammation.

Methods To see whether uric acid participates in acute lung inflammation, hydrochloric acid was injected into lungs of mice 3 days after commencement of continuous oral xanthine oxidase inhibitor febuxostat (FBX) treatment or of untreated C57BL/6 mice. Uric acid levels in serum and lung tissues were measured and neutrophilic response was assessed by quantification of inflammatory cells and measurement of tissue myeloperoxidase (MPO) activity.

Results Acid challenge raised uric acid levels in lung tissue (Figure) and induced neutrophil recruitment. FBX reduced uric acid levels in serum before acid challenge (1.18±0.13 (with FBX treatment, mg/dl), 2.6±0.30 (without FBX, mg/dl), p<0.05) and during inflammation (1.06±0.44 (with FBX, mg/dl), 2.8±0.68 (without FBX, mg/dl), p<0.05). There was a significant reduction in uric acid levels in acid-injured lung tissue by FBX treatment (13.5±6.4 (with FBX, μg/g lung), 30.3±11.8 (without FBX, μg/g lung), p<0.05). FBX blocked acute neutrophilic response to acid injection (neutrophil numbers; 4.42×10⁴ (with FBX), 1.16×10⁵ (without FBX), p<0.05). In mice treated with FBX, there was a significant reduction of MPO activity in lung tissue (36.77±29.80 (FBX), 68.64±43.06 (without FBX)).

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Conclusions Our results point to the contribution of uric acid in murine acid-induced lung inflammation.

References

1. Kono H, Chen CJ, Ontiveros F, Rock KL. Uric acid promotes an acute inflammatory response to sterile cell death in mice. The Journal of clinical investigation 2010;120: 1939-49.

2. Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nature reviews Rheumatology 2013;9: 13-23.

Disclosure of Interest None declared