Inflammatory responses to acute elevations of carbon dioxide in mice.

Health risks are described from elevated indoor air carbon dioxide (CO), 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 CO exhibit, respectively, 3.4 ± 0.9-fold (SE, = 6) and 4.1 ± 0.7-fold ( = 10) elevations in circulating microparticles (MPs); neutrophil and platelet activation, and vascular leak in brain, muscle, and distal colon. Interleukin (IL)-1β content of MPs also increases after 2,000 ppm by 3.8 ± 0.6-fold ( = 6) and after 4,000 ppm CO by 9.3 ± 1.1-fold ( = 10) greater than control. CO-induced vascular damage is abrogated by treating mice with an antibody to IL-1β or an IL-1β receptor inhibitor. Injecting naïve mice with CO-induced MPs expressing a protein found on mature neutrophils recapitulates vascular damage as seen with elevated CO, and destruction of MPs in CO-exposed mice abrogates vascular injuries without altering neutrophil or platelet activation. We conclude that environmentally relevant elevations of CO trigger neutrophils to generate MPs containing high concentrations of IL-1β that cause diffuse inflammatory vascular injury. Elevated levels of CO 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 CO were found to cause diffuse vascular damage because neutrophils are stimulated to produce microparticles that contain high concentrations of interleukin-1β.