title: High doses of intravenous immunoglobulin G enhance Kupffer cell phagocytic function during the late phase of sepsis and endotoxemia in rats.
abstract: The effect of intravenous immunoglobuln G (ivIG) on the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia in rats was studied by using in vivo microscopy. One hour after administration of a clinically relevant dose of ivIG (0.5 g/kg body weight, Sandoglobulin), rats were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP) or were injected intravenously with lipopolysaccharide (LPS, 0.1 mg/kg body weight). Twenty-four hours after CLP or LPS, the number of leukocytes adhering to the sinusoidal wall was increased 11.0-fold in CLP-treated animals and 5.6-fold in LPS-treated animals, respectively, compared with the controls. Concomitantly, the numbers of swollen sinusoidal endothelial cells were increased 4.2-fold and 3.2-fold. The number of perfused sinusoids was decreased by 35% and by 24%. These responses were minimized by pretreatment with high doses of ivIG. Kupffer cell phagocytic activity in the periportal sinusoids in CLP-treated animals was decreased by 41%, whereas that in the centrilobular sinusoids in LPS-treated animals was increased by 72%. IvIG significantly elevated this activity in both CLP- and LPS-treated animals and the number of ED2-positive Kupffer cells in tissue sections. The results suggest that ivIG limits the hepatic microvascular inflammatory response during the late phase of sepsis and endotoxemia by affecting Kupffer cell function.
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson 85724-5044, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: W
authors.initials: W
authors.lastname: Lukita-Atmadja
authors.forename: N W
authors.initials: NW
authors.lastname: Machen
authors.forename: G L
authors.initials: GL
authors.lastname: Baker
authors.forename: R S
authors.initials: RS
authors.lastname: McCuskey
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004727:Endothelium / Q000473:pathology; D019446:Endotoxemia / Q000276:immunology / Q000628:therapy*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007416:Intestinal Perforation / Q000150:complications; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008833:Microcirculation; D009504:Neutrophils / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology / Q000628:therapy*
chemical_list: D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides