ToxSci Advance Access first published online on June 9, 2005
This version published online on July 7, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi217
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1 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM. USA
* To whom correspondence should be addressed. Several studies have found that smoking cigarettes is a risk factor for systemic lupus erythematosus (SLE). To examine this issue in a mouse model, we subjected preautoimmune MRL-lpr/lpr mice for 4 weeks to cigarette smoke to provide standardized smoke effluents equivalent to moderate or to heavy smoking habits for people. The spontaneous production of IgG anti-chromatin but not IgM anti-chromatin, anti-denatured DNA or rheumatoid factor antibodies was lower in mice exposed to 250 mg/m3 particulates from mainstream smoke, and this suppression of autoimmunity was sustained for 8 weeks (p<0.02). In contrast to control mice anti-chromatin activity in smoke-exposed mice began to increase in 16-week-old mice, reaching levels at 6 months that were 2-3-fold higher than controls for IgG (p<0.03) and 10- fold higher for IgM (p<0.001). There was no significant effect on total IgG or IgM. In newly diagnosed SLE patients, smoking was negatively correlated with IgG anti-DNA antibodies (p<0.03). However, of 9 patients who discontinued smoking prior to diagnosis, 8 had elevated IgG anti-DNA compared to 29/79 never smokers and 9/31 smokers (p<0.01 compared to former smokers). Inhaled cigarette smoke appears to have a long- lasting immunsuppressive effect on T cell dependent autoimmune responses although autoantibodies increase to supra-elevated levels after the suppressive effect has abated.
Received March 3, 2005
Accepted May 27, 2005
Immunotoxiocology
Effect of Cigarette Smoke on Autoimmunity in Murine and Human Systemic Lupus Erythematosus
2 Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM, USA
3 Lovelace Respiratory Research Institute, Albuquerque, NM., USA
4 College of Pharmacy Toxicology Program, University of New Mexico Health Sciences Center, Albuquerque, NM. USA
5 Departments of Internal Medicine and Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM. USA
Robert L. Rubin, E-mail: rlrubin{at}salud.unm.edu
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