Local expression of cytokines has been implicated in the chronic inflammation of rheumatoid disease in both adults and children. IL-1β, IL-6, IL-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) are found in rheumatoid synovial effusions or are expressed by rheumatoid synoviocytes. We have hypothesized that the deposition or in situ formation of immune complexes may be important initiators of inflammation in juvenile rheumatoid arthritis (JRA). These studies were undertaken to examine the inflammatory potential of JRA synovial fluid immune complexes by examining their capacity to induce cytokine expression from normal leukocytes.

Synovial fluid from 3 children with JRA, 2 with pauciarticular JRA and one with polyarticular disease, was used for these studies. The IgG fraction from all 3 samples was prepared by affinity chromatography on Protein A agarose. In addition, 2 of the samples (1 from a child with polyarticular disease and 1 from a child with pauciarticular disease) were subjected to size-exclusion chromatography on Sephacryl-300. Material eluted from the S-300 column was divided into a high molecular weight fraction (“Fx 1”) and 4 fractions of decreasing molecular weight (“Fx2-5”). The synovial fluid IgG fractions (25 - 50 μg ml) were then incubated with 1 ×[Illegible Text] fresh human peripheral blood mononuclear cells (PBMC's) for 72 hrs. Culture supernates were collected and IL-1β, IL-6, IL-8, and GM-CSF concentrations measured by ELISA.

IgG fractions from all 3 synvoial fluid samples induced IL-1β, IL-6, IL-8, and GM-CSF from PBMC's. The fractions of highest molecular weight(“Fx1-2”) were the most potent inducers of cytokine secretion: levels of all 4 cytokines were equivalent to those produced by unopsonized BSA-anti-BSA immune complexes. In contrast, cytokine concentrations induced by the lower molecular weight fractions were equivalent to those achieved with monomeric human IgG.

Our data demonstrate that high molecular weight synovial fluid IgG fractions are potent inducers of a proinflammatory cytokine response. These findings strongly support a role for such complexes in the pathogenesis of chronic synovial inflammation seen in JRA.