Previously, we observed in a rat model that
intravenous administration of intramuscular
immunoglobulin preparations induced a long-lasting
hypotension, which appeared to be associated with the presence of
IgG polymers and dimers in the preparations, but unrelated to complement activation. We found evidence that this hypotensive response is mediated by
platelet-activating factor (PAF) produced by macrophages. In this study, we compared the vasoactive effects of 16
intravenous immunoglobulin (
IVIG) products from 10 different manufacturers, in anesthetized rats. Eight of the
IVIG preparations showed no hypotensive effects (less than 15% decrease), whereas the other 8 had relatively strong effects (15%-50% decrease). The hypotensive effects correlated with the
IgG dimer content of the preparations. Pretreatment of the rats with recombinant
PAF acetylhydrolase completely prevented the hypotensive reaction on
IVIG infusion, and administration after the onset of
hypotension resulted in normalization of the blood pressure. We also observed PAF production on in vitro incubation of human neutrophils with
IVIG, which could be blocked by anti-Fcgamma receptor
antibodies. This indicates that induction of PAF generation may also occur in a human system. Our findings support the hypothesis that the clinical side effects of
IVIG in patients may be caused by macrophage and neutrophil activation through interaction of
IgG dimers with Fcgamma receptors. Because phagocyte activation may also lead to the release of other inflammatory mediators, recombinant
PAF acetylhydrolase (rPAF-AH) provides a useful tool to determine whether PAF plays a role in the clinical side effects of
IVIG. If so, rPAF-AH can be used for the treatment of those adverse reactions. (Blood. 2000;95:1856-1861)