© 2005 American Thoracic Society
We thank Drs. Thom, Weaver, and Hampson for their comments in response to our recent report highlighting the antiinflammatory effects of inhaled CO in an animal model of ventilator-induced lung injury (1). The toxicity of CO is well known and we agree entirely with the authors' references to this issue, especially given their significant contributions to the field of CO poisoning. Our laboratory is not focused on studying CO poisoning, but rather in the past 5 years has concentrated on studies to better understand the potential biological effects of CO. This initial interest in the biological function of CO arose from the intriguing paradigm that the heme oxygenase system can generate CO endogenously ( The writers of the letter comment that "many of the ‘protective effects’ of CO are intriguing, though sometimes not clearly distinguished from the cellular effects of lowering tissue oxygen tension, and are sometimes not reproducible in other laboratories" (2); this is an unfair statement and somewhat misleading to the scientific community. A fair argument should always present both sides of the coin, and the authors were remiss in not referencing or acknowledging the more than 20 published papers from at least 10 independent laboratories (3–8) in the past 5 years that support the paradigm that CO is cytoprotective in both in vitro and in vivo models of cellular and tissue injury when used in similar or slightly higher concentrations than those in our study (1). We are not stating that the overwhelming evidence of studies supporting these cytoprotective effects of CO (3–8) will ultimately prove that CO can be therapeutically administered to humans as a viable treatment modality. Only time will tell. We agree that the potential application of CO to human diseases will depend on a more comprehensive understanding of the toxicity, pharmacokinetics, and biology of CO, used at low concentrations. We are aware of three ongoing human clinical trials for various pathophysiologic disease states where inhaled CO is administered at concentrations similar to those used by us (1). Although it is unknown what results these studies will yield, we can continue to strive for additional and new knowledge to "tempt" us to speculate that some day inhaled CO could serve as a therapeutic modality in human diseases. Obviously, to translate this temptation into reality will require further rigorous investigations, but as scientists we should not stop dreaming of new therapeutic modalities to fight against human diseases.
a University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania REFERENCES
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10 ml/day of exhaled CO).