Published ahead of print on July 17, 2008, doi:10.1165/rcmb.2008-0107OC
© 2009 American Thoracic Society DOI: 10.1165/rcmb.2008-0107OC Adjuvant and Anti-Inflammatory Properties of Cigarette Smoke in Murine Allergic Airway Inflammation1 Medical Sciences Program, 2 Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, 3 Department of Medicine, Division of Respirology, McMaster University, Hamilton, Ontario, Canada Correspondence and requests for reprints should be addressed to Martin R. Stämpfli, McMaster University, Department of Pathology and Molecular Medicine, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada. E-mail: stampfli{at}mcmaster.ca The impact of cigarette smoke on allergic asthma remains controversial both clinically and experimentally. The objective of this study was to investigate, in a murine model, how cigarette smoke affects immune inflammatory processes elicited by a surrogate allergen. In our experimental design, mice were concurrently exposed to cigarette smoke and ovalbumin (OVA), an innocuous antigen that, unless introduced in the context of an adjuvant, induces inhalation tolerance. We show that cigarette smoke exposure has adjuvant properties, allowing for allergic mucosal sensitization to OVA. Specifically, concurrent exposure to cigarette smoke and OVA for 2 weeks led to airway eosinophilia and goblet cell hyperplasia. In vivo OVA recall challenge 1 month after the last smoke exposure showed that concurrent exposure to OVA and cigarette smoke induced antigen-specific memory. Robust eosinophilia and OVA-specific IgG1 and IgE characterized the ensuing inflammatory response. Mechanistically, allergic sensitization was, in part, granulocyte macrophage colony-stimulating factor (GM-CSF) dependent, as a significant reduction in BAL eosinophilia was observed in mice treated with an anti–GM-CSF antibody. Of note, continuous smoke exposure attenuated the OVA recall response; decreased airway eosinophilia was observed in mice continuously exposed to cigarette smoke compared with mice that ceased the smoke exposure protocol. In conclusion, we demonstrate experimentally that while cigarette smoke acts as an adjuvant allowing for allergic sensitization, it also attenuates the ensuing eosinophilic inflammatory response.
Key Words: cigarette smoke • adjuvant • antiinflammatory • allergic airway eosinophilia • murine models
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