Association between cigarette smoking and release of tumour necrosis factor alpha and its soluble receptors by peripheral blood mononuclear cells in patients with rheumatoid arthritis

Rheumatology (Oxford). 2006 Oct;45(10):1223-9. doi: 10.1093/rheumatology/kel094. Epub 2006 Apr 3.

Abstract

Objective: To investigate the relationship between cigarette smoking and release of TNF-alpha and its soluble receptors (sTNFRI and sTNFRII) by peripheral blood mononuclear cells (PBMCs) from RA patients.

Methods: We studied 71 RA patients with established disease (mean duration 10.6 yr). Smoking history was established by questionnaire. T lymphocytes and monocytes were isolated from peripheral blood and incubated with or without stimulation (phytohaemagglutinin and lipopolysaccharide, respectively). Release of TNF-alpha and sTNFR into culture medium was measured by enzyme-linked immunosorbent assay.

Results: TNF-alpha release by stimulated T lymphocytes was significantly higher in patients with a history of smoking than in those who had never smoked (1416.0 vs 767.4 pg/ml, P = 0.04), and showed a relationship with smoking duration and intensity (P for trend < or =0.009). Monocyte TNF-alpha release was not associated with smoking status. Release of sTNFR showed no clear relationships with extent of smoking, although release by stimulated T lymphocytes was higher in past smokers than in those who had never smoked (P < or = 0.03). The ratio of TNF-alpha/sTNFR released from T lymphocytes was higher in past and current smokers, and was associated with extent of smoking. No relationship was found between smoking and plasma TNF-alpha levels, but levels of both receptors were higher in past smokers.

Conclusion: In RA patients who smoke there is an alteration in the ratio of TNF-alpha/sTNFR released by stimulated T cells that might favour increased TNF-alpha activity. The increased TNF-alpha/sTNFR ratio is associated with extent of smoking, and remains elevated after smoking cessation.

MeSH terms

  • Analysis of Variance
  • Arthritis, Rheumatoid / immunology*
  • Case-Control Studies
  • Cells, Cultured
  • Humans
  • Leukocytes, Mononuclear / immunology*
  • Lymphocyte Activation
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor / immunology*
  • Receptors, Tumor Necrosis Factor, Type I / blood
  • Receptors, Tumor Necrosis Factor, Type I / immunology
  • Receptors, Tumor Necrosis Factor, Type II / blood
  • Receptors, Tumor Necrosis Factor, Type II / immunology
  • Smoking / immunology*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha