Intravenous immunoglobulin G (IVIG) inhibits IL-1- and TNF-α-dependent, but not chemotactic-factor-stimulated, neutrophil transendothelial migration

High-dose intravenous immunoglobulin (IVIG) has anti-inflammatory effects via incompletely understood mechanisms. By investigating whether IVIG might modulate neutrophil (PMN) recruitment, we observed that IVIG dose-dependently inhibited (by 30–50%) PMN transendothelial migration (TEM) across human umbilical vein endothelial cells (EC) stimulated with IL-1α, IL-1β, TNF-α or IL-1β + TNF-α. Inhibition required the presence of IVIG with the responding PMNs, was attributable to the F(ab)2 portion and was unrelated to putative contaminants in IVIG. IVIG did not inhibit IL-1β- or TNF-α-induced increase of PMN adhesion to EC, nor did it affect C5a- or IL-8-induced PMN TEM across unstimulated EC. Effects of IVIG and F(ab)2 fragments were not associated with PMN activation, assessed by CD62L shedding, CD11b upregulation or PMN shape. Thus, IVIG selectively inhibits PMN TEM across inflammatory-cytokine-stimulated – but not unstimulated – EC, perhaps contributing to therapeutic benefit in chronic inflammation with minimal impact on chemotactic-factor-induced PMN recruitment during acute infection.

► IVIG inhibited PMN migration across IL-1- and TNF-α-activated endothelium.
► Inhibition was dependent on presence of IVIG with PMNs and was mediated by F(ab)2 fragment.
► IVIG did not affect PMN adhesion to endothelium or transmigration induced by IL-8 or C5a.
► IVIG inhibition was not associated with PMN activation, siglec-9 antibody, FasL or HLA Class I.
► IVIG may modulate PMN recruitment in chronic, inflammatory-cytokine-mediated conditions