Intravenous immunoglobulin G selectively inhibits IL-1α-induced neutrophil-endothelial cell adhesion.
OBJECTIVE
Intravenous immunoglobulin (IVIG) G at high doses has therapeutic benefits in a variety of autoimmune and inflammatory disorders. The mechanism by which IVIG modulates inflammation is incompletely understood. We tested the hypothesis that IVIG modulates inflammation by inhibiting interactions between neutrophils and vascular endothelium, required for leukocyte recruitment to inflamed tissues.


METHODS
The adhesion of human blood neutrophils to resting or cytokine-activated human umbilical vein endothelial cells (HUVECs) was measured, and the effect of IVIG or normal donor sera added at various stages was determined.


RESULTS
IVIG completely inhibited neutrophil adhesion to endothelium stimulated with interleukin-1 (IL-1α), when it was present during the endothelial stimulation phase. IVIG had no effect on adhesion when IL-1β or TNF-α was the activating cytokine. The plasma of some (one of five) healthy donors also selectively blocked the IL-1α activation of the endothelium for supporting adhesion, and this was due to the presence of neutralizing IgG at high levels in the blood of the donor.


CONCLUSIONS
Thus, IgG antibodies to IL-1α are present in IVIG at a biologically significant level, which can prevent endothelial activation. However, IVIG does not directly affect activation of endothelium or neutrophil adhesion mechanisms. The anti-inflammatory properties of IVIG may in part be related to blocking IL-1α-dependent leukocyte recruitment. Potentially, such antibodies may also have immunoregulatory effects by binding and neutralizing membrane-bound IL-1α during cell-cell interactions.
Macmillan
Heather F
HF
Department of Pathology, Dalhousie University, Halifax, NS, Canada.
Rowter
Derek
D
Lee
Tim
T
Issekutz
Andrew C
AC
D002448:Cell Adhesion / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D053582:Interleukin-1alpha / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*
D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D053582:Interleukin-1alpha