Blocking the protein Granulocyte macrophage-colony stimulating factor (GM-CSF) can reduce or prevent cigarette smoke-induced lung inflammation in mice and may lead to new treatments for smoke-related disease, specifically chronic obstructive pulmonary disease (COPD).

The findings appear in the American Journal of Respiratory and Critical Care Medicine.

Cigarette smoke triggers the release of GM-CSF and other cytokines and chemokines which cause activation and recruitment of more inflammatory cells into the lung,thereby perpetuating the inflammatory response and exacerbating ongoing inflammation. These activated and recruited inflammatory cells also release proteases such as matrix metalloproteinase (MMP)-12, which destroy the lung tissue, resulting in emphysema.

The study revealed that blocking GM-CSF could reduce the inflammation and other deleterious effects of cigarette smoke exposure in mice.

A group of mice, half of which had been treated with a GM-CSF blocking agent, anti-GM-CSF, and half of which were controls, were exposed to the equivalent of nine cigarettes of smoke each day for four days. At the end of four days, the mice were killed and their lung tissue was examined for the presence of inflammatory cells.

"We found that anti-GM-CSF strongly reduced the number of potentially harmful white blood cells that infiltrate the lung after smoke exposure, as well as inhibiting the pro-inflammatory cytokine tumor necrosis factor (TNF)-, the chemokine macrophage inflammatory protein-2 (MIP-2), which coordinates the movement of white blood cells into the lung," said lead researcher on the study, Ross Vlahos, Ph.D., a senior research fellow at the University of Melbourne.

"The blocking agent also inhibited the protease MMP-12, which is known as one of the main enzymes able to destroy lung tissue."

The results are preliminary, but the researchers are optimistic about what may come of the study. "Short-term models often translate into benefits in longer-term models. We still need to develop new methods and agents to test this idea long term and we also need to learn if it is effective in reversing longstanding disease," explained Vlahos.

The research is also no excuse for smokers, the authors say. While the results may eventually lead to treatments for COPD, they do not address any of the other health risks associated with smoking.


Citation: Vlahos et al., 'Neutralizing GM-CSF Inhibits Cigarette Smoke-induced Lung Inflammation', Am. J. Respir. Crit. Care Med., March 2010; doi:10.1164/rccm.200912-1794O