ToxSci Advance Access originally published online on June 9, 2005
Toxicological Sciences 2005 87(1):86-96; doi:10.1093/toxsci/kfi217
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Effect of Cigarette Smoke on Autoimmunity in Murine and Human Systemic Lupus Erythematosus
* Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131; Department of Mathematics and Statistics, University of New Mexico, Albuquerque, New Mexico 87131; Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108; College of Pharmacy Toxicology Program, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131; and ¶ Departments of Internal Medicine and Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131
Received March 3, 2005; accepted May 27, 2005
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 pre-autoimmune 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 two- to three-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 nine patients who discontinued smoking prior to diagnosis, eight 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.
Key Words: immunotoxicology-autoimmune; inhalation toxicology; environmental toxicology.
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