Human il-38 reduces joint inflammation in a mouse model of gouty arthritis
1Experimental Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
2Department of Biochemistry and Molecular Genetics
3Department of Medicine, University of Colorado Denver, Aurora, USA
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
Citation: Ann Rheum Dis, volume 77, supplement Suppl, year 2018, page A135
Session: Fires and firefighters: switching the immune system on and off