Complement regulates the capacity of immune complexes to elicit cytokine secretion from leukocytes

Complement plays a critical role in the detoxification of immune complexes by regulating their size and facilitating their removal via C3b receptor-bearing cells. We demonstrate another consequence of complement opsonization: the regulation of cytokine responses from leukocytes. Immune complexes were formed in the presence ("opsonized complexes ") or absence ("unopsonized camplexes") of serum and purified by on Protein A-agarose. Complexes were incubated with human peripheral blood mononuclear cells (PBMC's) or U937 cells for 72 hours. Concentrations of IL-1β, IL-6, IL-8, and GM-CSF in the cell culture supernates were measured by ELISA. Complement reduced the capacity of immune complexes to stimulate cytokine secretion in both cell types. Opsonized immune complexes were 30% less effective in inducing IL-1β and 40% less effective in inducing IL-8 from PBMC's and U937 cells (neither IL-6 nor GM-CSF were detected in U937 cell supernates). Opsonized complexes were 40% less effective than unopsonized in inducing IL-6 and 70% less effective in inducing GM-CSF from PBMC's. Thus, complement opsonization reduces the phlogistic potential oflC's.