Effect of intravenous immunoglobulin G on the TNFalpha-mediated hepatic microvascular inflammatory response.
The effect of intravenous immunoglobulin G (ivIG) on the hepatic microvascular inflammatory response elicited by tumor necrosis factor alpha (TNFalpha) in rats was studied by means of in vivo microscopy and histological examination. One hour after the portal infusion of TNFalpha, the average number of leukocytes adhering to the sinusoidal endothelium was increased sevenfold, and the average number of the perfused sinusoids was decreased by 15% when compared with controls. Concomitantly, the expression of intercellular adhesion molecule-1 (ICAM-1) on the hepatic sinusoidal endothelium and that of the central vein was increased. The phagocytic activity of Kupffer cells in centrilobular sinusoids was increased by 54%, as were the number of ED2-positive Kupffer cells in tissue sections. Pretreatment with a clinically relevant high dose of ivIG (1 g/kg body weight, Sandoglobulin) minimized these responses by reducing leukocyte-endothelial interactions and Kupffer cell phagocytic function. The results suggest that high doses of ivIG limit the hepatic microvascular inflammatory response by inhibiting the action of the proinflammatory cytokine TNFalpha.
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Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson 85724-5044, USA.
Lukita-Atmadja
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Machen
N W
NW
Baker
G L
GL
McCuskey
R S
RS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D006520:Hepatitis, Animal / Q000188:drug therapy / Q000378:metabolism*; D007074:Immunoglobulin G / Q000494:pharmacology*; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1