Contribution of mast cell-derived interleukin-1β to uric acid crystal-induced acute arthritis in mice.

OBJECTIVE Gouty arthritis is caused by the precipitation of monosodium urate monohydrate (MSU) crystals in the joints. While it has been reported that mast cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs during acute attacks of gout. This study was undertaken to assess the role of MCs in a mouse model of MSU crystal-induced acute arthritis. METHODS We assessed the effects of intraarticular (IA) injection of MSU crystals in various strains of mice with constitutive or inducible MC deficiency or in mice lacking interleukin-1β (IL-1β) or other elements of innate immunity. We also assessed the response to IA injection of MSU crystals in genetically MC-deficient mice after IA engraftment of wild-type or IL-1β(-/-) bone marrow-derived cultured MCs. RESULTS MCs were found to augment acute tissue swelling following IA injection of MSU crystals in mice. IL-1β production by MCs contributed importantly to MSU crystal-induced tissue swelling, particularly during its early stages. Selective depletion of synovial MCs was able to diminish MSU crystal-induced acute inflammation in the joints. CONCLUSION Our findings identify a previously unrecognized role of MCs and MC-derived IL-1β in the early stages of MSU crystal-induced acute arthritis in mice.