Submitted on September 19, 2007
Accepted on June 19, 2008
High Dose but not Low Dose Mainstream Cigarette Smoke Suppresses Allergic Airway Inflammation by Inhibiting T Cell Function
Thomas H Thatcher1, Randi P. Benson2, Richard P Phipps3, and Patricia J Sime4*
1 Pulmonary and Critical Care Medicine, University of Rochester, Rochester, New York, United States
2 Environmental Medicine, University of Rochester, Rochester, New York, United States
3 Dept. of Environmental Medicine and the Lung Biology and Disease Program, University of Rochester, Rochester, New York, United States
4 Pulmonary and Critical Care Medicine, Box 692, University of Rochester Medical Center, Rochester, New York, United States
* To whom correspondence should be addressed. E-mail: patricia_sime{at}urmc.rochester.edu.
Epidemiological studies have identified childhood exposure to environmental tobacco smoke as a significant risk factor for the onset and exacerbation of asthma, but studies of smoking in adults are less conclusive, and mainstream cigarette smoke (MCS) has been reported to both enhance and attenuate allergic airway inflammation in animal models. We sensitized mice to ovalbumin (OVA), and exposed them to MCS in a well-characterized exposure system. Exposure to MCS (600 mg/m3 total suspended particulates, TSP) for 2 hours per day suppresses the allergic airway response, with reductions in eosinophilia, tissue inflammation, goblet cell metaplasia, IL-4 and IL-5 in BALF, and OVA-specific antibodies. Suppression is associated with a loss of antigen-specific proliferation and cytokine production by T cells. However, exposure to a lower dose of MCS (77 mg/m3 TSP) had no effect on the number of BAL eosinophils or OVA-specific antibodies. This is the first report to demonstrate, using identical smoking methodologies, that MCS inhibits immune responses in a dose-dependent manner, and may explain the observation that, although smoking provokes a systemic inflammatory response, it also inhibits T cell-mediated responses involved in a number of diseases.
