Inflammatory responses to acute elevations of carbon dioxide in mice

Health risks are described from elevated indoor air carbon dioxide (CO2), which often ranges from 1,000 to 4,000 ppm, but the mechanisms are unknown. Here, we demonstrate that mice exposed for 2 h to 2,000 or 4,000 ppm CO2 exhibit, respectively, 3.4 +/- 0.9-fold (SE, n = 6) and 4.1 +/- 0.7-fold (n = 10) elevations in circulating microparticles (MPs); neutrophil and platelet activation, and vascular leak in brain, muscle, and distal colon. Interleukin (IL)-1 beta content of MPs also increases after 2,000 ppm by 3.8 +/- 0.6-fold (n = 6) and after 4,000 ppm CO2 by 9.3 +/- 1.1-fold (n = 10) greater than control. CO2-induced vascular damage is abrogated by treating mice with an antibody to IL-1 beta or an IL-1 beta receptor inhibitor. Injecting naive mice with CO2-induced MPs expressing a protein found on mature neutrophils recapitulates vascular damage as seen with elevated CO2, and destruction of MPs in CO2-exposed mice abrogates vascular injuries without altering neutrophil or platelet activation. We conclude that environmentally relevant elevations of CO2 trigger neutrophils to generate MPs containing high concentrations of IL-1 beta that cause diffuse inflammatory vascular injury. NEW & NOTEWORTHY Elevated levels of CO2 are often found in indoor air and cause adverse health effects, but the mechanisms have not been identified. In a murine model, environmentally relevant levels of CO2 were found to cause diffuse vascular damage because neutrophils are stimulated to produce microparticles that contain high concentrations of interleukin-1 beta.