Diagnosis of an exposure to airborne toxicants can be problematic.
Phosgene is used widely in industry for the production of many synthetic products, such as polyfoam rubber, plastics, and
dyes. Although nearly 100% of the gas is consumed during processing, there is the potential problem of accidental or even intentional exposure to this
irritant/
choking agent. Exposure to
phosgene has been known to cause latent life-threatening
pulmonary edema. A major problem is that there is a clinical latency phase from 3 to 24 h in people before irreversible
acute lung injury occurs. Assessment of markers of
acute lung injury after a suspected exposure would be useful in developing rational treatment strategies. These experiments were designed to assess bronchoalveolar lavage fluid (BALF) for the presence of the early markers of exposure to
phosgene in mice from 1 to 72 h after exposure. Separate groups of 40 CD-1 male mice (Crl:CD-1(ICR)BR) weighing 29 +/- 1 g were exposed whole-body to either air or a concentration x time (c x t) amount of 32 mg/m(3) (8 ppm)
phosgene for 20 min (640 mg x min/m(3)). BALF from air- or
phosgene-exposed mice was taken at 1, 4, 8, 12, 24, 48, and 72 h postexposure. After
euthanasia, the trachea was excised, and 800 micro l saline was instilled into the lungs and washed 5x. BALF was assessed for
interleukin (IL)-4,
IL-6,
tumor necrosis factor (
TNF) alpha, IL-1alpha,
macrophage inflammatory protein (MIP)-2, and
IL-10. At 4 h postexposure,
IL-6 was 15-fold higher for
phosgene-exposed mice than for the time-matched air-exposed control group. At 8 and 12 h,
IL-6, IL-1beta, MIP-2, and
IL-10 were significantly higher in
phosgene-exposed mice than in time-matched air-exposed controls, p < or = 0.05 to p < or = 0.001, whereas
TNF alpha reached peak significance from 24 to 72 h.
IL-4 was significantly lower in the
phosgene-exposed mice than in the air-exposed mice from 4 to 8 h after exposure. These data show that BALF is an important tool in assessing pro- and anti-inflammatory markers of
phosgene-induced
acute lung injury and that knowledge of these temporal changes may allow for timely treatment strategies to be applied.