Dr Danielle Morse from the University of Pittsburgh School of Medicine was awarded a grant from the GEMI Fund in 2003 to do research on the role of carbon monoxide in pulmonary fibrosis. This is a brief summary of her findings.
Dr Danielle Morse and her research group researched the role of carbon monoxide in pulmonary fibrosis (scarring), looking particularly at idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis is an incurable fibrosing disorder, restricting the amount of air that reaches the bloodstream, that progresses relentlessly to respiratory failure. Life expectancy of patients after diagnosis with IPF is rarely longer than five years. Having worked with acute lung injuries previously and observed carbon monoxide interventions in action, Dr Morse hypothesized that a product of heme oxygenase activity, carbon monoxide (CO), could have anti-fibrotic effects.
Fibrosis represents an important response to tissue injury. In the lung, however, excessive fibrosis can lead to impairment of gas exchange and ultimately respiratory failure. No intervention has been demonstrated to reverse fibrosis in the human lung, and there are few therapies
that show promise for slowing or halting the progression of fibrosis.
Carbon monoxide (CO) is a biologically active molecule produced by the human body both in health and disease. There is evidence in that it can exert protective effects in lung injury and transplantation. In addition, CO has well described anti-proliferative properties so Dr Morse and her group chose to test whether it could protect against lung fibrosis in vivo and if it could inhibit fibroplast proliferation in vitro.
Fibrosis in mice was induced using bleomycin, a chemotherapeutic drugantibiotic that can cause pulmonary fibrosis and impaired lung function. The effects of CO administration were then examined. Mice exposed to CO showed a significantly lesser degree of fibrosis, even with short, transient exposure to the gas.
To test these effects in vitro, cultured human lung fibroplasts were exposed to CO at 250 ppm; exposure to the gas significantly inhibited fibrobplast proliferation.
Dr Danielle Morse and her group’s GEMI-funded research demonstrated that low-concentration inhaled CO can inhibit the pulmonary fibrotic response in a bBleomycin rodent model. It is postulated that one of the mechanisms for this action could be the inhibition of fibroblast proliferation but the mechanism by which CO exerts this effect remains to be further elucidated. Further investigation of this mechanism will provide a starting point for future studies of the effect of CO on fibrosis and fibroblast behaviour. For the approximately five million people worldwide affected by pulmonary fibrosis, it could represent a first step towards relief.