To determine whether levels of
interleukin (IL)-18, together with those of IL-1beta,
tumor necrosis factor-alpha,
IL-6, and
IL-8, are elevated in the plasma of patients with
gouty arthritis, the plasma concentrations of those
cytokines were measured in 31 males with
gouty arthritis. Further, CD14+ cells were obtained from human blood and thioglycolate medium-induced peritoneal cells obtained from
caspase 1-deficient mice, and then separately cultured in the presence of
monosodium urate monohydrate (MSU) crystals. In addition, in an animal in vivo experiment, MSU crystals were injected into subcutaneous air pouches of IL-18-deficient mice. The plasma concentrations of
IL-18,
IL-6, and
IL-8 were elevated in the presence of
gouty arthritis in the
gout patients. In the in vitro study, the presence of MSU crystals stimulated CD14+ cells (monocytes) to secrete
IL-18 and increased the activity of
caspase 1 in CD14+ cells, whereas there was no significant effect on
IL-18 messenger RNA in CD14+ cells and only a slight induction of
IL-18 secretion from thioglycolate medium-induced
caspase 1-deficient peritoneal cells. In the in vivo experiment, MSU crystals injected into the air pouch promoted neutrophil accumulation along with an increase in concentrations of keratinocyte-derived
chemokine (KC) and
macrophage inflammatory protein (MIP)-1alpha in air-pouch fluids in both IL-18-deficient and wild-type mice. However, there was no increase in the concentration of
IL-18 in air-pouch fluids in either mouse strain. Our results suggest that plasma
IL-18,
IL-6,
IL-8, and
C-reactive protein (CRP) levels reflect local
inflammation associated with
gouty arthritis, though
IL-18 does not play an important role in neutrophil accumulation. Further, they suggest that MSU crystals accelerate the processing of
IL-18 from an inactive to active form via the activation of
caspase 1.