HUMAN INTRAVENOUS IMMUNOGLOBULIN (IVIG) PREPARATIONS DEGRANULATE HUMAN NEUTROPHILS IN-VITRO

IVIG preparations have biological effects in: vivo that are not fully understood. Possible effects include the property to stimulate Fe rece ptors on various cell types. To study whether IVIG may interact with n eutrophils we developed an in vitro system, in which neutrophils, in w hole blood or purified, were incubated with IVIG and assessed for degr anulation by measuring the release of elastase and lactoferrin in cult ure medium. All commercially available IVIG preparations tested induce d degranulation of neutrophils when incubated for 2 h at therapeutical ly relevant concentrations. In studies with blocking antibodies agains t Pc receptors (FcR), this degranulation was shown to be dependent on Fc gamma RII, whereas Fc gamma RIII had no effect. Experiments with pu rified neutrophils as well as binding experiments with labelled IVIG p reparations indicated that neutrophil degranulation resulted from a di rect interaction of IVIG with neutrophils. Using gel filtration fracti ons, it was found that polymeric and dimeric Ige present in NTG was ma inly responsible for the degranulation. We suggest that degranulation of neutrophils may contribute to the (side)effects of IVIG treatment i n vivo.