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OP0170 Human il-38 reduces joint inflammation in a mouse model of gouty arthritis
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  1. D.M. De Graaf1,
  2. F.L. Van de Veerdonk1,
  3. E.Z. Eisenmesser2,
  4. L.A.B. Joosten1,
  5. C.A. Dinarello1,3
  1. 1Experimental Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
  2. 2Department of Biochemistry and Molecular Genetics
  3. 3Department of Medicine, University of Colorado Denver, Aurora, USA

Abstract

Background Interleukin-38 (IL-38) is the last member of the IL-1 family of cytokines to be fully investigated for its functions. IL-38 is proposed as an anti-inflammatory cytokine in various auto-inflammatory diseases, such as psoriasis and rheumatoid arthritis. For example, IL-38 knockout mice have exacerbated autoantibody-induced arthritis. Current understanding of the capacity of IL-38 in gout, a prototype IL-1β driven auto-inflammatory disease, is unknown.

Objectives We hypothesised that in vivo treatment with human recombinant IL-38 results in a reduction in join inflammation in a mouse model of gouty arthritis.

Methods We treated C57/Bl6 mice with 1 µg recombinant IL-38 (3–152 AA) intraperitoneally at 24, 12 and 2 hours before induction of gouty arthritis with intra-articular injection of albumin-opsonized monosodium urate crystals (300 µg) and palmitic acid (200 µM) in 10 µL PBS. Joint inflammation was scored after 4 hours. The synovial lining was cultured in RPMI for 2 hours to allow cytokines to be secreted, and cytokines in the synovium were extracted with Triton-X 100 to obtain total cytokines (membrane and intracellular). In the synovial culture fluid and extract, IL-1β, IL-6 and KC were measured by ELISA. Data

Results Mice treated with recombinant IL-38 exhibited significantly reduced joint swelling and redness on a three-point macroscopic inflammation scale: Vehicle-treated 1.5±0.25 vs IL-38 Treated 0.75+0.25 (n=10, p<0.0001, Mann Whitney-U test). The 2 hour synovial membrane culture fluid contained significantly lower levels of IL–1β (1207±480 vs 379±184 pg/mL, p<0.05), IL-6 (10783±2490 vs 5321±2935 pg/mL, p<0.05) and KC (4390±931 vs 1081±750 pg/mL, p<0.05). In extract of the synovial membrane, there is a reduction in IL–1β (1505±397 vs 624±509 pg/mL, p<0.05), IL-6 (11059±2299 vs 3597±2509 pg/mL, p<0.01) and KC (1505±397 vs 624±509 pg/mL, p<0.05).

Conclusions Human recombinant IL-38 reduces swelling and redness of the joint, and pro-inflammatory cytokines secreted by and contained in the synovial membrane in a mouse model of gouty arthritis. These data reveal that recombinant IL-38 has therapeutic benefit in an IL–1β mediated model of inflammation.

Disclosure of Interest None declared

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