P156/O08\u2005Systemic inflammation originating from the skin or the intestine combined with biomechanical stress has different effects on the joints in an in vivo mouse model

Abstract

Career situation of first and presenting author Post-doctoral fellow. Introduction Psoriasis (PsO) and inflammatory bowel disease (IBD) share a wide range of comorbidities, including psoriatic arthritis (PsA). Entheses, the attachment sites of tendons and ligaments into the bones, spread the mechanical forces generated by movement onto the bone and are considered as a primary disease localization in PsA. Increasing evidence supports the hypothesis that biomechanical stress, together with inflammatory triggers from distant sites, such as the skin or the intestine, can contribute to the onset of PsA by inducing microdamage in the entheses. Objectives In this study, we aimed to investigate the role of biomechanical stress together with cutaneous or intestinal inflammation in initiating joint disease. Methods Eight-week-old male C57/Bl6 mice were treated with imiquimod cream (IMQ) on a shaved area of the back skin or with dextran sodium sulphate (DSS) dissolved in the drinking water to induce PsO-like skin or IBD-like gut inflammation. Control mice were left untreated. Afterwards, half of the mice were subject to a forced treadmill running protocol to increase biomechanical stress. Control mice with or without IMQ or DSS treatment did not run. Severity of cutaneous or intestinal inflammation was assessed clinically and by histology; knees and paws were analyzed by microCT, histology and immunohistochemistry. Results Local induction of cutaneous or intestinal inflammation led to a systemic response, as detected by splenomegaly, trabecular subchondral bone loss and bone marrow hypercellularity. On a background of PsO- but not of IBD-like inflammation, discrete signs of synovitis determined by the presence of CD45+ cells\u2009and overexpression of IL-17 were detected, with no significant impact of the running protocol. The CD45+ cells in the IMQ non-running condition were identified as F4/80+cells, in contrast to the running condition where the CD45+ cells\u2009could not be further identified, showing negative results for F4/80, CD3, MPO and MCSF-R stainings. Furthermore, forced exercise and PsO-like inflammation both induced overexpression of IL-17 at the entheses and acted synergistically when combined. Conclusions Local induction of PsO- or IBD-like inflammation triggers a systemic response with inflammation-associated bone loss and discrete signs of joint disease. PsO-like inflammation in combination with biomechanical stress increased the degree of synovitis and enthesitis, showing that systemic inflammation combined with biomechanical stress may contribute to disease manifestations in PsA. Disclosure of Interest G. Gulino: None declared, M. Van Mechelen: None declared, R. Lories Consultant for: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer, UCB.