The role of interleukin-8 and other cytokines in the pathogenesis of Felty's syndrome

OBJECTIVE: Felty's syndrome (FS) is defined as rheumatoid arthritis (RA) with neutropenia and, in some cases, splenomegaly; the outcome is primarily determined by the risk of infection, which is related to the degree of neutropenia. We analysed whether the clinical manifestations of FS, especially neutropenia, could be explained by abnormalities in cytokine production. METHODS: We examined the production in FS of five cytokines involved in the maturation and activation of polymorphonuclear cells (PMNs): IL-1 beta, TNF alpha, IL-8, G-CSF and GM-CSF. Because of the role of systemic IL-8 in neutrophil migration, serum IL-8 levels were also evaluated. RESULTS: Spontaneous and anti-CD16 stimulated cytokine production was similar in FS, RA and healthy controls (NC). However, anti-CD3 stimulated IL-8 production was significantly increased compared to NC in both RA and FS. FS patients who spontaneously produced G-CSF in culture were protected from bacterial infections. Serum IL-8 levels were elevated in FS and RA compared to NC (p < 0.001 for both groups). In FS, serum IL-8 was higher in patients with a history of bacterial infections compared to those without (p < 0.01) and there was a weak inverse correlation between neutropenia and serum IL-8 levels (Kendal's tau B = -0.31, p = 0.05). CONCLUSION: The neutropenia of FS cannot be explained by changes in peripheral blood cytokine production, although changes in the bone marrow microenvironment cannot be excluded. Our data do suggest a possible role for G-CSF and IL-8 in the development of certain FS complications.