PMID- 20380586
OWN - NLM
STAT- MEDLINE
DCOM- 20110301
LR  - 20101111
IS  - 1607-842X (Electronic)
IS  - 0891-6934 (Linking)
VI  - 43
IP  - 8
DP  - 2010 Dec
TI  - Intravenous immunoglobulin G selectively inhibits IL-1alpha-induced 
      neutrophil-endothelial cell adhesion.
PG  - 619-27
LID - 10.3109/08916931003599062 [doi]
AB  - OBJECTIVES: 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-1alpha), when it was present during the endothelial 
      stimulation phase. IVIG had no effect on adhesion when IL-1beta or TNF-alpha was the 
      activating cytokine. The plasma of some (one of five) healthy donors also 
      selectively blocked the IL-1alpha 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-1alpha 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-1alpha-dependent leukocyte recruitment. Potentially, 
      such antibodies may also have immunoregulatory effects by binding and 
      neutralizing membrane-bound IL-1alpha during cell-cell interactions.
FAU - Macmillan, Heather F
AU  - Macmillan HF
AD  - Department of Pathology, Dalhousie University, Halifax, NS, Canada.
FAU - Rowter, Derek
AU  - Rowter D
FAU - Lee, Tim
AU  - Lee T
FAU - Issekutz, Andrew C
AU  - Issekutz AC
LA  - eng
GR  - MG 7684/Canadian Institutes of Health Research/Canada
GR  - MGC 57081/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100412
PL  - England
TA  - Autoimmunity
JT  - Autoimmunity
JID - 8900070
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Interleukin-1alpha)
SB  - IM
MH  - Cell Adhesion/*immunology
MH  - Endothelium, Vascular/cytology/*immunology
MH  - Humans
MH  - Immunoglobulin G/blood
MH  - Immunoglobulins, Intravenous/*pharmacology
MH  - Inflammation/drug therapy/*immunology
MH  - Interleukin-1alpha/*immunology
MH  - Neutrophils/cytology/*immunology
EDAT- 2010/04/13 06:00
MHDA- 2011/03/02 06:00
CRDT- 2010/04/13 06:00
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2011/03/02 06:00 [medline]
AID - 10.3109/08916931003599062 [doi]
PST - ppublish
SO  - Autoimmunity. 2010 Dec;43(8):619-27. doi: 10.3109/08916931003599062. Epub 2010 
      Apr 12.