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FRI0034 Taurine chloramine inhibition of cytokine secretion by rheumatoid adipose tissue and synovial membrane explants
  1. E. Kontny1,
  2. M. Plebanczyk1,
  3. P. Maldyk2,
  4. W. Maslinski1,
  5. J. Marcinkiewicz3
  1. 1Department of Pathophysiology and Immunology
  2. 2Department of Rheumoorthopedic Surgery, Institute of Rheumatology, Warsaw
  3. 3Department of Immunology, Jagiellonian University Medical College, Cracow, Poland

Abstract

Background Our previous data have proved that taurine chloramine (Tau-Cl), an endogenous molecule formed in activated neutrophils, normalizes pathological functions of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS)[1-3]. Moreover, we have recently reported that rheumatoid articular adipose tissue (AAT) produces factors activating FLS and thus may contribute to local pathological processes [4]. It is likely that Tau-Cl generated by infiltrating neutrophils may also affect cytokine secretion by joint-associated adipose tissue but this suggestion has not been verified yet.

Objectives To evaluate Tau-Cl effects on the production of select cytokines by rheumatoid synovial membrane (SM), AAT and subcutaneous periarticular adipose tissue (ScAT) explants.

Methods Tissue specimens were obtained from the knee joints of 64 patients with established RA who were undergoing total joint replacement surgery. Tissue explants (100 mg/ml/well) were treated for 18 h with 1 μg/ml of lipopolysaccharide (LPS) from Escherichia coli 055:B5 in the presence or absence of Tau-Cl (500 μM). After the treatment concentrations of select pro- (IL-1β, TNF, IL-6, IL-8) and anti-inflammatory (IL-10 and interleukin 1 receptor antagonist - IL-1Ra) cytokines were measured by specific ELISA. The Wilcoxon test was applied to evaluate the effects of LPS and Tau-Cl, while comparison between AAT, ScAT and SM cultures was done using Mann-Whitney U test.

Results Both AAT and ScAT produced spontaneously smaller amounts of all tested cytokines than SM. LPS vigorously raised release of cytokines from both adipose tissues with the fold increase within the range 10 - 20 for IL-1β, IL-1Ra, IL-6, and IL-8 or 50 - 100 for TNF and IL-10, while its stimulatory effect on SM was less pronounced (the fold increase within the range 2-20 and 30-40, respectively). Despite this, LPS-treated SM explants still released more cytokines than AAT and ScAT. In LPS-treated adipose tissues cultures Tau-Cl potently inhibited production of IL-1β, IL-6 and IL-1Ra but exerted weaker inhibitory effects on TNF and IL-8 release (% of inhibition within the range 60-70 and 25-30, respectively). In LPS-treated SM cultures Tau-Cl had no effect on TNF and IL-1Ra secretion but down-regulated IL-1β by 50%, while IL-6 and IL-8 by 25-30%. Importantly, Tau-Cl did not affect LPS-triggered IL-10 secretion by any tested tissues.

Conclusions We report for the first time that Tau-Cl is a potent inhibitor of pro-inflammatory cytokine secretion by joint-associated adipose tissues. Although this compound exerts weaker inhibitory effect on the release of pro-inflammatory cytokines by SM, its net local effect could be anti-inflammatory due to sparing IL-10 production and inhibition of mostly IL-1β (SM) or both IL-1β and IL-1Ra (AAT and ScAT). Thus, our results expand the spectrum of known anti-inflammatory activities of Tau-Cl and give further support to consider this compound as a promising candidate for RA treatment.

  1. Kontny E et al., Arthritis Rheum., 2000, 43:2169-2177.

  2. Kontny E et al., Inflamm Res., 2006, 55:446-455.

  3. Kontny E et al., Amino Acids 2007, 32:447-452.

  4. Kontny E et al., Ann Rheum Dis., 2012, 71:262-267.

Disclosure of Interest None Declared

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