These findings suggest that drugs that block the activity of ICAM-1 could be used to prevent radiation therapy-related problems, conclude Dennis E. Hallahan, M.D., and his colleagues at Vanderbilt University in Nashville, Tenn.

Therapeutic chest irradiation often results in complications such as radiation pneumonitis (lung inflammation), pulmonary fibrosis (the accumulation of collagen, or scar tissue, in the lungs), and respiratory insufficiency (diminished lung performance). These problems limit the ability of physicians to effectively treat lung cancer using radiation.

Earlier studies suggested that acute inflammation could be prevented in radiation-treated mice that were genetically engineered to lack ICAM-1, a cell adhesion molecule that mediates the recruitment of leukocytes, or white blood cells, to the lungs. Leukocytes contribute to inflammation, which leads to fibrosis and decreased lung performance. However, it remains unclear whether blocking ICAM-1 expression can also prevent fibrosis and respiratory insufficiency.

To determine the role of ICAM-1 in pulmonary fibrosis and lung performance, Hallahan and his coworkers treated groups of 10 mice with either mock irradiation or with varying doses of radiation to the thorax. Some of the mice were genetically engineered to lack the ICAM-1 gene, while others had a normal ICAM-1 gene. The researchers measured the degree of lung inflammation, fibrosis, and decreased lung performance in the groups of mice.

Lungs of mice that lacked the ICAM-1 gene had markedly fewer infiltrating leukocytes, whose presence indicates inflammation, at all radiation doses compared with t
'"/>

Contact: Linda Wang
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute
14-May-2002