Rheumatology Advance Access originally published online on April 3, 2006
Rheumatology 2006 45(10):1223-1229; doi:10.1093/rheumatology/kel094
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Association between cigarette smoking and release of tumour necrosis factor 
and its soluble receptors by peripheral blood mononuclear cells in patients with rheumatoid arthritis
1Staffordshire Rheumatology Centre, University Hospital of North Staffordshire and 2Institute of Science and Technology in Medicine, Keele University, Keele, UK.
Correspondence to: D. L. Mattey, Staffordshire Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire ST6 7AG, UK. E-mail: Derek.Mattey{at}uhns.nhs.uk
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Abstract |
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Objective. To investigate the relationship between cigarette smoking and release of TNF-
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- and sTNFR into culture medium was measured by enzyme-linked immunosorbent assay.
Results. TNF- 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 
0.009). Monocyte TNF- 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 0.03). The ratio of TNF-/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- 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-/sTNFR released by stimulated T cells that might favour increased TNF- activity. The increased TNF-/sTNFR ratio is associated with extent of smoking, and remains elevated after smoking cessation.
KEY WORDS: Smoking, Tumour necrosis factor, Tumour necrosis factor receptors, Mononuclear cells, Rheumatoid arthritis.
Submitted 28 November 2005;
revised version accepted 17 February 2006.
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