Gout as autoinflammatory disease: new mechanisms for more appropriated treatment targets

Abstract

Gout is probably one of the oldest diseases affecting men. This is not surprising especially for the active role that innate immunity seems to play in its pathogenesis. It is fascinating to observe as this ancestral mechanism of defense feels that microcrystals are a danger, quite similar to infectious agents. New advances have revealed that at the base of the powerful inflammatory reaction stimulated by monosodium urate crystals there are many complexes cellular mechanisms, mainly involving inflammasome and toll-like receptors. Subsequently, there is an early increase of proinflammatory cytokines responsible for the acute attack, followed in few days by their reduction along with an increase of anti-inflammatory cytokines, probably main actors of the resolution phase. New targets have also been identified for the reduction of hyperuricemia, the prerequisite of gout, in order to prevent new attacks and the deposition of urate crystals in and around the joints. All these aspects, leading to deeper insight, have suggested new treatments, some of which are already available while others are likely to become available in the near future.