Smoking and Air Pollution as Pro-Inflammatory Triggers for the Development of Rheumatoid Arthritis

Nicotine Tob Res. 2016 Jul;18(7):1556-65. doi: 10.1093/ntr/ntw030. Epub 2016 Mar 8.


Introduction: Smoking is now well recognized not only as a risk factor for rheumatoid arthritis (RA), but also as a determinant of disease activity, severity, response to therapy, and possibly mortality.

Methods: Studies, mostly recent, which have provided significant insights into the molecular and cellular mechanisms which underpin the pathogenesis of smoking-related RA, as well as the possible involvement of other types of outdoor and indoor pollution form the basis of this review.

Results: Smoking initiates chronic inflammatory events in the lungs. These, in turn, promote the release of the enzymes, peptidylarginine deiminases 2 and 4 from smoke-activated, resident and infiltrating pulmonary phagocytes. Peptidylarginine deiminases mediate conversion of various endogenous proteins to putative citrullinated autoantigens. In genetically susceptible individuals, these autoantigens trigger the production of anti-citrullinated peptide, pathogenic autoantibodies, an event which precedes the development of RA.

Conclusions: An increasing body of evidence has linked chronic inflammatory events in the lungs of smokers, to the production of anti-citrullinated peptide autoantibodies and development of RA. Creation of awareness of the associated risks, assessment of smoking status and implementation of compelling antismoking strategies must be included in the routine clinical management of patients presenting with suspected RA.

Implications: Chronic inflammatory mechanisms operative in the lungs of smokers lead to the production of anti-citrullinated protein antibodies which, in turn, drive the development of RA. These mechanistic insights not only reinforce the association between smoking and risk for RA, but also the necessity to increase the level of awareness in those at highest risk.

Publication types

  • Review

MeSH terms

  • Air Pollution / adverse effects*
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / prevention & control
  • Citrulline / metabolism*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Hydrolases
  • Lung / metabolism*
  • Middle Aged
  • Models, Biological
  • Protein Processing, Post-Translational
  • Protein-Arginine Deiminases
  • Smoking / adverse effects*


  • Citrulline
  • Hydrolases
  • Protein-Arginine Deiminases