Interleukin-8 (IL-8) is a member of the so-called c-x-c chemokine family which is important in the immunopathology of rheumatoid disease. IL-8 plays a role in the recruitment of neutrophils to the synovial space and in the induction of angiogenesis in the synovial panus. We have previously demonstrated the presence of soluble immune complexes in synovial effusions of children with juvenile rheumatoid arthritis (JRA). The current studies were undertaken to determine whether soluble immune complexes can induce IL-8 expression from leukocytes.

BSA-anti-BSA immune complexes were formed in the presence (opsonized complexes) or absence (unopsonized complexes) of serum and purified on Protein A-agarose. Complexes or monomeric IgG (25-100 μg/ml) were added to peripheral blood mononuclear cells (PBMC's) or U937 cells (1× 106 cells/condition) for 72 hours. IL-8 concentrations were measured by ELISA.

Soluble immune complexes induced IL-8 from U937 cells and PBMC's in a dose-dependent fashion. PBMC's produced higher concentrations of IL-8 than U937 cells. For example, at 50 μg/ml, unopsonized complexes produced 247± 140 pg/ml IL-8, while in PBMC's concentrations were 106 ± 16 ng/ml. Complement opsonization reduced the capacity of the complexes to induce IL-8 by 35-40% in both cell types. Thus, IL-8 concentrations were 65 ± 38 ng/ml. when 50 μg/ml opsonized complexes were used with PBMC's and 164± 4 pg/ml with U937 cells.

Cycloheximide completely inhibited IL-8 secretion, demonstrating that IL-8 expression required new protein biosynthesis. Northern blots detected IL-8 mRNA within one hour after incubation of the cells with immune complexes, and was still present 12 hours later. IL-8 expression was not dependent upon the expression of IL-1: incubation of the cells with IL-1 receptor antagonist(IL-1ra) had no effect on IL-8 secretion.

We conclude that soluble, unopsonized immune complexes are potent inducers of IL-8 in leukocytes. This finding is consistent with the hypothesis that such complexes are directly involved in the pathogenesis of chronic synovial inflammation in JRA.