Immune complex-mediated cytokine production is regulated by classical complement activation both in vivo and in vitro

Immune complexes (IC) induce a number of cellular functions, including the enhancement of cytokine production from monocytes, macrophages and plasmacytoid dendritic cells. The range and the composition of cytokines induced by IC in vitro is influenced by the availability of an intact classical complement cascade during cell culture, as we have showed in our studies on artificial IC and on cryoglobulins purified from patients with lymphoproliferative diseases. When IC purified from systemic lupus erythematosus sera were used to stimulate in vitro cytokine production, the amount of circulating IC and IC-induced cytokine levels depended both on in vivo classical complement function as well as on the occurrence of anti-SSA, but not on anti-dsDNA or any other autoantibodies. Collectively these findings illustrate that studies on IC-induced cytokine production in vitro requires stringent cell culture conditions with complete control and definition of access to an intact classical complement pathway in the cell cultures. If IC are formed in vivo, the results have to be interpreted in the context of classical complement activation in vivo as well as the occurrence of IC-associated autoantibodies at the time of serum sampling.