Polyvalent immunoglobulin for intravenous use interferes with cell proliferation in vitro

Intravenous immunoglobulin is used to an increasing extent in various immune-mediated diseases, but its mechanism(s) of action in vivo is incompletely understood. Previous studies have shown that intravenous immunoglobulin may interfere with autoantibodies and their production by B cells and also inhibit Fc-mediated antibody-dependent cytotoxicity. Here we describe a novel effect of intravenous immunoglobulin on proliferation of in vitro activated peripheral blood lymphocytes and autonomously growing cell lines of various origin. Independently of whether proliferation was autonomous or induced by antigen-specific or antigen-nonspecific reagents, proliferation was inhibited in a dose-dependent fashion, as measured by reduced 3H-thymidine and BrdU uptake and cell counting. The effect was not due to cytotoxic effects of intravenous immunoglobulin and was reversible after removing the intravenous immunoglobulin by washing. The IgG levels required for this inhibition of proliferation are supraphysiological but are reached in vivo during treatment with intravenous immunoglobulin.