Non-Hyperuricemia Experimental Models of Gout

Gout is the most common form of inflammatory arthritis in men, driven by hyperuricemia and the deposition of monosodium urate (MSU) crystals. The innate immune response to these crystals leads to acute inflammatory episodes, called flares, characterized by intense joint pain, swelling, and temporary disability. Although gout flares are self-limiting, they impose a considerable burden on patients’ quality of life and contribute to increased healthcare utilization. A detailed understanding of the inflammatory processes triggered by MSU crystals is critical for developing targeted therapies to prevent and manage flares effectively. This review provides an overview of experimental models used to study the inflammatory phase of gout, with a focus on both in vivo and in vitro models of MSU crystal-induced inflammation. We concentrate on models that reproduce the acute inflammatory response following MSU crystal deposition, including the air pouch, intraarticular injection, and peritonitis rodent models, alongside the larval zebrafish model. In addition, we discuss in vitro approaches using primary immune cells and cell lines. We discuss the strengths, limitations, and translational relevance of these models and highlight some examples of how they have contributed to our understanding of the etiology of gout. Of note, models of hyperuricemia are not included here as these have been extensively reviewed elsewhere.