Crystal-Associated Inflammation: Some Mechanisms of Cellular Activation

Abstract

Acute inflammation in association with crystals of monosodium urate is thought to be mediated by the presence of polymorphonuclear leucocytes (PMN) both in acute gouty arthritis and in experimentally induced crystal arthritis. Support for this hypothesis includes the massive accumulation of PMN in inflamed synovium and synovial fluid, the striking diminution of experimentally induced urate crystal synovitis following neutrophil depletion by cytotoxic drugs [1] or PMN-specific anti-serum [2] and the clinical effect of colchicine, a drug which inhibits many PMN functions [3]. Acute gouty arthritis can, however, occur in the absence of neutrophile [4], and some more recent studies have focussed on the potential role of monocytes [5, 6], resident macrophages, fibroblasts [7] and synoviocytes [8] as cells which could be responsible for the initial induction and chronic pathology in urate-crystal-mediated inflammation. Increasingly, evidence is pointing to a central role for soluble cytokines such as interleukin (IL)-1 [7], IL-6 [9], IL-8 [10] and tumour necrosis factor α (TNF-α) as mediators of urate-crystal-induced inflammation and tissue damage.