Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

This article is part of the supplement: 25th European Workshop for Rheumatology Research

Poster presentation

Identification of a natural soluble form of the IL-18 receptor accessory protein as an immunomodulator in experimental arthritis

RL Smeets, OJ Arntz, MB Bennink, WB van den Berg and FAJ van de Loo

Author affiliations

Experimental Rheumatology and Advanced Therapeutics, Department of Rheumatology, University Medical Center Nijmegen, The Netherlands

For all author emails, please log on.

Citation and License

Arthritis Research & Therapy 2005, 7(Suppl 1):P89  doi:10.1186/ar1610

The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Background

In the inflammatory process preceding erosive arthritis, IL-18 plays an important role. IL-18 is known to regulate immune responses by stimulating Th1 maturation, and signaling is initiated through formation of a trimeric receptor complex, consisting out of IL-18 bound to the IL-18Rα and its accessory receptor IL-18Rβ.

Objective

The aim of this study was to determine the physiological role of a recently described soluble form of the IL-18 receptor accessory protein (sIL-18Rβ) in mice.

Methods

Mouse sIL-18Rβ (genebank accession number AK053176) was cloned from murine lung cDNA and used for the generation of an adenoviral vector (Ad.5IL-18Rβ). Expression analysis of the sIL-18Rβ and its full-length membrane bound IL-18Rβ in different murine tissue was achieved through endpoint PCR. To investigate the in vivo mode of action, sIL-18Rβ was systemically overexpressed in collagen type II-immunized male DBA/1 mice. Systemical overexpression was achieved through intravenous injection of 3 × 108 pfu Ad5sIL-18Rβ or the control vector (Ad5Luc) before clinical manifestation of collagen-induced arthritis (CIA). At 1 and 4 days post adenoviral injection, splenocytes were harvested and the cytokine profile in plasma and splenocyte culture supernatants was determined

Results

Short IL-18Rβ mRNA was highly expressed in tissue of lymphoid origin, and no expression could be observed in immune privileged organs like the testis, the eye and the brain, suggesting a prominent role in immune regulation. Expression of sIL-18Rβ was disease regulated in mice suffering from CIA, whereas the full-length IL-18Rβ was not regulated. Splenocytes of sIL-18Rβ-treated immunized mice produced significantly less interferon gamma and IL-10 compared with control treated animals. Adenoviral overexpression of the sIL-18Rβ before clinical manifestation of CIA significantly aggravated arthritis, which was accompanied by a reduction of circulating IL-10, interferon gamma and a significant increased anti-bovine collagen II IgG1.

Conclusion

Our results describe the existence of a novel short soluble form of the membrane IL-18Rβ, which is mainly expressed in lymphoid tissues. This sIL-18Rβ expression appears regulated during CIA. Furthermore, we show that this novel soluble IL-18Rβ functions as a putative modulator of IL-18 signaling; aggravating CIA, by modulating T-cell immunity.