Assessment of the molecular basis of the proallergenic effects of cigarette smoke

Epidemiological studies indicate a link between smoking and increased risk of immunoglobulin E-mediated allergies and asthma. The molecular basis unde rlying cigarette smoke related respiratory disorders are ill defined, but i t is known that mast cells in the mucosal lining of the airways are an impo rtant reservoir of proinflammatory mediators, which play a pivotal role in the development of these diseases. The establishment of a novel cell exposu re unit facilitated a study of mast cell responses to pollutants in mainstr eam cigarette smoke at the air/cell interface. Our study shows that cigaret te smoke, but not filtered clean air, induces the release of mediators of t ype I hypersensitivity responses and stimulates the synthesis of proinflamm atory cytokines, including interleukin (IL)-4, 5, 10, and 13 and tumor necr osis factor (INF)-alpha, in cells of mast cell lineage. These results expla in how exposure to pollutants present in cigarette smoke can induce the pat hophysiological responses associated with allergy, IgE-mediated and IgE-ind ependent asthma since IL-4 and IL-13 induce class switching to IgE, and IL- 13 has recently been identified as the key mediator of IgE-independent asth ma.