The activity of pulmonary indoleamine 2,3-dioxygenase in rats and mice is not altered by oxygen exposure.

We tested the hypothesis that pulmonary indoleamine 2,3-dioxygenase (indole:oxygen 2,3-oxidoreductase (decyclizing), EC 1.13.11.17), an enzyme that consumes superoxide anion (O-2), might have an antioxidant role under conditions of hyperoxia. We measured indoleamine 2,3-dioxygenase in three experimental models in which pulmonary superoxide dismutase, catalase and glutathione peroxidase (the known antioxidant enzymes) show increased activity and are associated with greater tolerance to 96-98% O2 exposure: (1) adult rats preexposed to 85% O2 for 5-7 days; (2) neonatal rats exposed directly to greater than 95% O2; and (3) adult rats treated with bacterial endotoxin during O2 exposure. Indoleamine 2,3-dioxygenase did not increase in response to O2 exposure in any of these rat models. Conversely, in adult mice treated with endotoxin, lung indoleamine 2,3-dioxygenase activity did increase, but no protection against O2 toxicity occurred. Thus, a rise in indoleamine 2,3-dioxygenase is neither necessary nor sufficient to confer resistance to O2 toxicity. These data taken together are evidence against its having any important role in the antioxidant defense system of the lung.