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This article is part of the supplement: 6th Global Arthritis Research Network (GARN) Meeting

Poster presentation

Regulation of eicosanoid production in peripheral blood mononuclear cells from patients with systemic sclerosis

Otylia Kowal-Bielecka1, Krzysztof Kowal2, Justyna Chwiecko1, Stanislaw Sierakowski1, Oliver Distler3, Sylwia Chwiesko1, Izabela Domyslawska1 and Steffen Gay3

Author affiliations

1 Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Poland

2 Department of Allergology and Internal Medicine, Medical University of Bialystok, Poland

3 Center of Experimental Rheumatology, University Hospital, Zurich, Switzerland

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Citation and License

Arthritis Research & Therapy 2007, 9(Suppl 3):P13  doi:10.1186/ar2239

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/9/S3/P13


Published:19 October 2007

© 2007 BioMed Central Ltd

Background

Eicosanoids are arachidonic acid-derived mediators that play a key role in the regulation of inflammatory response. 5-Lipoxygenase (5-LOX)-derived leukotrienes are considered proinflammatory while 15-lipoxygenase (15-LOX)-derived products such as 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins inhibit proinflammatory mediators including leukotrienes, and actively participate in the resolution of inflammation. It has been demonstrated that a temporal switch of arachidonic acid metabolism from predominant 5-LOX-derived to 15-LOX-derived products is crucial for the resolution of inflammation. We have recently shown that there is an imbalance between proinflammatory leukotrienes and anti-inflammatory lipoxins in the lungs of patients with systemic sclerosis (SSc)-related interstitial lung disease, which may favour chronic inflammation and fibrosis [1,2].

Objective

To further investigate the role of eicosanoids in the pathogenesis of SSc through evaluation of: (1) the basal profile of eicosanoid synthesis, and (2) the pattern of eicosanoid biosynthesis in response to proinflammatory stimuli by peripheral blood mononuclear cells (PBMC) from patients with SSc in comparison with healthy people.

Methods

Mononuclear cells were isolated from peripheral blood using density gradient centrifugation on Lymphoprep and cultured in fetal calf serum-supplemented RPMI medium at 37°C under 5% CO2. Ionophore-stimulated production of 5-LOX-derived leukotriene E4 (LTE4) and 15-LOX-derived 15-HETE was evaluated by means of enzyme immunoassay at predefined time points in basal conditions (without stimuli) as well as in response to TNFα. Ten patients with SSc (five diffuse and five limited cutaneous SSc) as well as five healthy controls were studied.

Results

There were no significant differences in the basal production of LTE4 or 15-HETE between SSc patients and healthy controls. TNFα induced sequential changes in the production of eicosanoids, with an early (within 1 hour) increase in LTE4 followed by a delayed increase in 15-HETE in both SSc patients and healthy controls. PBMC from SSc patients responded to TNFα with significantly higher production of LTE4 in comparison with healthy controls (P < 0.05 at 1 hour), while there were no significant differences in TNFα-induced production of 15-HETE between SSc patients and controls.

Conclusion

These preliminary results of our study indicate that the TNFα-induced eicosanoid synthesis is altered in PBMC from patients with SSc. Increased production of proinflammatory leukotrienes may contribute to the pathogenesis of SSc.

References

  1. Kowal-Bielecka O, Distler O, Kowal K, et al.: Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage fluid from patients with scleroderma lung disease.

    Arthritis Rheum 2003, 48:1639-1646. PubMed Abstract | Publisher Full Text OpenURL

  2. Kowal-Bielecka O, Kowal K, Distler O, et al.: Cyclooxygenase- and lipoxygenase-derived eicosanoids in bronchoalveolar lavage fluid from patients with scleroderma lung disease: an imbalance between proinflammatory and antiinflammatory lipid mediators.

    Arthritis Rheum 2005, 52:3783-3791. PubMed Abstract | Publisher Full Text OpenURL