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THU0066 Smoking functions as a negative regulator of IGF-1 levels and activates the cascade of adipokine signaling molecules in patients with rheumatoid arthritis
  1. R. Doria Medina,
  2. M. Erlandsson,
  3. S. Lindblad Silfverswärd,
  4. M. Bokarewa
  1. Rheumatology and Inflammation Research, University of Göteborg, Göteborg, Sweden

Abstract

Background Cigarette smoking has been recently connected to the pathogenesis of rheumatoid arthritis (RA). The cellular mechanisms and molecular events initiated by smoking and leading to severe inflammation, low efficacy of anti-rheumatic drugs, and autoantibody production, are still poorly understood. Adipokines are signalling molecules originating from adipose tissue and regulating carbohydrate and lipid metabolism. In RA, adipokines are connected to inflammation, disease activity and radiological signs of joint destruction. Effects of adipokines are mediated through insulin receptor/insulin-like growth factor-1 receptor (IGF-1R) complex.

Objectives Present study evaluates a link between cigarette smoking, IGF-1 signalling and adipokine cascade in patients with rheumatoid arthritis.

Methods One hundred-eleven patients (76 women, 35 men) with established RA (mean disease duration 9.9 years) participated in the structured telephone interview on their smoking habits. Patients were stratified by smoking habits, age, and levels of IGF-1. Levels of adipokines (visfatin, adiponektin, resistin and leptin) were analyzed in blood samples of these patients using commercial ELISAs.

Results Thirty-three of 111 patients (29.7%) reported to be current smokers, while 78 patients were non-smokers. Smokers had slightly shorter disease duration and had a prevalence of men, while disease activity, erosivity and presence of RF were similar between the smokers and non-smokers. Smokers had lower levels of IGF-1 compared to non-smokers (median: 2.64 vs 8.08, p=0.035). Levels of IGF-1 are inversely related to age, this enabled distinct analysis of the younger (mean age 50 y, n=62) and older (mean age 69 y, n=49) patient groups. Smoking was associated with low levels of IGF-1 in the younger (5.82 vs 11.12, p=0.030) and in the older patients (1.05 vs 4.28 ng/ml, p=0.05). Levels of adipokines were similar in the total group of smokers and non-smokers, however IGF-1 was inversely related to visfatin levels (r=-0.35, p=0.003). In the absence of IGF-1 stimulation in patients with low levels of IGF-1, visfatin correlated to resistin (r=0.599) and leptin (r=0.450) levels. No such correlation within adipokine network was found in patients with high levels of IGF-1.

Direct inhibitory effect of nicotine on IGF-1 levels was proved in mice. Mice supplemented with nicotine (0.02-0.05%) in drinking water had significantly lower levels of IGF-1 in blood compared to their siblings drinking pure water (p=0.0007). Treatment of mice with recombinant IGF-1 resulted in significantly low circulating levels of leptin, visfatin and resistin.

Conclusions Smoking functions as a negative regulator of IGF-1 levels in RA patients and has repressive effects on the cascade of adipokine signaling molecules, contributing to inflammation and joint destruction in RA.

Disclosure of Interest None Declared

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