【Introduction】To date, several animal arthritis models such as Collagen-Induced Arthritis (CIA) and Adjuvant-Induced Arthritis (AIA) have been established. However, as there are diverse clinical subtypes in auto-immune diseases, these arthritis models can’t recapitulate all the auto-immune diseases, especially, auto-inflammatory syndrome, which is characterized by poly-arthritis in large joints, rash, fever and elevated white blood cells. Recently, IL-1 is implicated in the pathogenesis of auto-inflammatory syndrome. In this study, we generate new model mice and identify a therapeutic target.
【METHODS/RESULTS】We successfully generated conditional transgenic mice of human IL-1 (IL-1 cTg), in which human IL-1α was driven under a Cre/loxP system, in a C57/BL6 background. Arthritis development in large joints was seen in all IL-1 cTg mice one week after polyIpolyC administration with a 100% success rate under a C57/BL6 background, which is a difficult strain to develop arthritis. Micro CT analysis demonstrated the joint destructions in large joints in IL-1 cTg mice. Elevated white blood cell counts, dermatitis, and splenomegaly, all of which were characteristic phenotypes of auto-inflammatory syndrome, were detected in these mice. We found that serum IL-6 levels were elevated in those mice by a cytokine assay. Thus, IL-1 cTg mice were crossed with IL-6 knockout (IL-6 KO) mice to yield IL-1 cTg/IL-6 KO. Interestingly, the phenotypes seen in the IL-1 cTg mice were recovered in IL-1 cTg/IL-6 KO.
【conclusion】We successfully generated a new auto-inflammatory syndrome model, and showed that IL-6 may represent a therapeutic target to this syndrome.