Stand-alone cytokines IL4 and IL10 have been succesfully used in preclinical models for inflammatory disease but yielded disappointing results in phase 2 clinical studies. We reasoned that this may have been due to poor bioavailability and lack of synergistic effects with other anti-inflammatory cytokines. To solve these issues we developed a fusion protein of IL4 and IL10, IL4-10 synerkine. The synerkine suppressed proinflammatory cytokine production in multiple in vitro assays, while unaffecting or increasing production of anti-inflammatory mediators, which effects were mediated by both cytokine moieties. Moreover, it improved cartilage metabolism in vitro. In vivo the synerkine normalized hyperalgesia in multiple animal models including carrageenan induced inflammatory pain in mice and osteoarthritis pain in dogs. Therefore, the IL4-10 synerkine seems a promising therapeutic option for inflammatory pain.
Disclosure of Interest None declared