Intravenous immunoglobulin attenuates the hepatic microvascular inflammatory response to TNF-alpha

The effect of intravenous immunoglobuln G (ivIG) on the hepatic microvascul ar inflammatory response elicited by tumor necrosis factor alpha (TNF-alpha ) in rats was studied by means of in vivo microscopy and histological exami nation. One hour after the portal infusion of TNF-alpha, the number of leuk ocytes adhering to the sinusoidal endothelium was increased 6-fold in perip ortal regions and and 7-fold in centrilobular regions when compared with co ntrols. The number of the perfused sinusoids was decreased by 17 % in perip ortal region and by 14 % in centrilobular regions. Concomitantly, the expre ssion of intercellular adhesion molecule-1 (ICAM-1) on the hepatic sinusoid al endothelium and that of the central vein was increased. The phagocytic a ctivity of Kupffer cells in centrilobular sinusoids was increased by 54 % a s were the number of ED2 positive Kupffer cells in tissue sections. Pretrea tment with a clinically relevant high dose of ivIG (1 g/kg body weight, San doglobulin) minimized these responses by reducing leukocyte-endothelial int eractions and Kupffer cell phagocytic function. The results suggest that hi gh doses of ivIG limit the hepatic microvascular inflammatory response by i nhibiting the action of the proinflammatory cytokine,TNF-alpha.