Effect of cigarette smoke on autoimmunity in murine and human systemic lupus erythematosus

Robert L. Rubin, Tracee M. Hermanson, Edward J. Bedrick, Jacob D. McDonald, Scott W. Burchiel, Mathew D. Reed, Wilmer L. Sibbitt

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)86-96
Number of pages11
JournalToxicological Sciences
Volume87
Issue number1
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Environmental toxicology
  • Immunotoxicology-autoimmune
  • Inhalation toxicology

ASJC Scopus subject areas

  • Toxicology

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