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Gout is a common form of inflammatory arthritis that is caused by the precipitation of monosodium urate crystals (MSU) in the joints. The acute form of gout is associated with sudden painful inflammatory episodes characterised by a large infiltration of neutrophils. The involvement of monocytes and macrophages is also recognised to be important, although the exact roles of monocytes and macrophages in gout need to be clarified. The overall objective of this thesis was to investigate the contributions of neutrophils, monocytes and macrophages to acute gouty inflammation. To determine whether the presence of other cells may be affecting neutrophil activation in gout inflammation, human blood neutrophils were stimulated with MSU as a purified population and in a mixed white blood cell population. The half-life of neutrophils in culture increased from 10h in purified neutrophil cultures to &gt;24h in mixed cell cultures. The increase in viability was associated with large increases in cytokine production (TNF[alpha], IL-1[Beta], IL-6, IL-8) in mixed cell cultures. Exposure of neutrophils to media conditioned by MSU-stimulated mononuclear cells improved both neutrophil viability and stimulated the IL-8 production from neutrophils to a greater extent than direct contact with MSU. Exposure to conditioned media also primed MSU-stimulated neutrophil superoxide responses. High superoxide production was also observed when serum was lowered to

Cellular Inflammation in Models of Acute Gout