OP0262 Disease modifying effects of the canine il4–10 fusion protein in the canine groove model of osteoarthritis
Authors: E.M. Van Helvoort, J. Popov-Celeketic, K. Coeleveld, A. Doornenbal, M. Tryfonidou, C. Wijne, F. Lafeber, S. Mastbergen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> An ideal disease modifying osteoarthritis (OA) drug should have analgesic, chondroprotective and anti-inflammatory effects. A fusion protein of Interleukin 4 and 10 (IL4–10FP) might have these effects. <h3>Objectives</h3> This study evaluates the effects of canine IL4–10FP (cIL4–10FP) in the canine Groove model of OA. <h3>Methods</h3> In 8 skeletally mature dogs, knee OA in the right leg was induced according to the Groove model. After 6 weeks of OA development, intra-articular injections in the affected knee with either PBS (500 µl; n=4) or cIL4–10FP (10 µg/500 µl; n=4) were given weekly for 10 weeks. The contra-lateral joints served as a healthy control. Force plate analysis (FPA) was used to determine joint loading as a surrogate marker of pain. The ratio of the affected over the contra-lateral control joint was calculated for each dog for each time point. FPA was performed before OA induction to determine baseline values, and before and 24 hours after the 1 st, 6th and 9th intra-articular injection. A linear mixed model was used to evaluate effects of injections. After 10 weeks of treatment dogs were euthanized and tissue samples were harvested. Serum Immunoglobulin G (IgGs) titers against cIL4–10FP were evaluated to check for potential antibody formation. Cartilage proteoglycan content and release of proteoglycans were determined <i>ex vivo</i> by Alcian Blue assay. Synovial inflammation was evaluated by HE-staining using OARSI grading. Changes in outcomes in the affected/treated joints compared to contra-lateral control joints were calculated. <h3>Results</h3> After OA induction a clear reduction in joint loading (increase in pain) was found (standing force and braking force). After cIL4–10FP injections these forces increased toward normalisation (cIL4–10FP vs PBS group, p=0.002 and p=0.01, respectively). No IgG elevation was detected after 10 injections. Compared to contra-lateral controls, proteoglycan content of OA PBS injected knees suggested tissue degeneration (27 vs 34 mg/g). In the cIL4–10FP treated group proteoglycan content in right knees was not different from the contralateral controls (33 vs 31 mg/g). The mean change in proteoglycan content compared to contra-lateral controls was different with a p value of 0.057 (figure 1). A similar pattern was found for the change in release of proteoglycans from the cartilage, which was less increased in the cIL4–10FP group compared to the PBS group (0.4% vs 3.0%; p=0.029, figure 1). Synovial inflammation was mild (characteristic of this model) and did not change after intra-articular injections (0.4 and −1.3 points out of 18 for cIL4–10FP and PBS respectively). <h3>Conclusions</h3> Repetitive intra-articular injection with canine IL4–10FP in dogs did not lead to antibody formation. Dogs treated with cIL4–10FP showed improved joint loading compared to PBS treated dogs, reflecting an analgesic effect. Recovery of proteoglycan content and normalisation of release in cIL4–10FP treated dogs indicate a chondroprotective effect. Synovial inflammation in the Groove model was too mild to be changed significantly. These results clearly warrant further research to develop IL4–10FP as a DMOAD. <h3>Acknowledgements</h3> This work is supported by the Dutch Arthritis Foundation project NR12–2–202 <h3>Disclosure of Interest</h3> None declared