Effect of cigarette smoke on autoimmunity in murine and human systemic lupus erythematosus.
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 immunosuppressive effect on T-cell-dependent autoimmune responses, although autoantibodies increase to supra-elevated levels after the suppressive effect has abated.
Rubin
Robert L
RL
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA. rlrubin@salud.unm.edu
Hermanson
Tracee M
TM
Bedrick
Edward J
EJ
McDonald
Jacob D
JD
Burchiel
Scott W
SW
Reed
Mathew D
MD
Sibbitt
Wilmer L
WL
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000943:Antigens, Differentiation / Q000502:physiology; D015551:Autoimmunity; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D053594:Myeloid Differentiation Factor 88; D009538:Nicotine / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000502:physiology; D012907:Smoking / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000974:Antibodies, Antinuclear; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; D009538:Nicotine