Altered serum cytokines in hepatic and portal blood of rats at early times following portal venous infusion of semi-allogeneic cells

Abstract

The liver of anaesthetized adult (>350 g) Lewis rats was perfused in vitro after cannulation of both the hepatic and portal vein, with clamping of the hepatic artery. Heparinized blood (400 μl) was withdrawn at 0, 6, 12, 18, 24, 30 and 36 h from each site, and serum and peripheral blood lymphocytes (PBL) isolated after ficoll/hypaque separation. Serum was tested in bioassays for cytokines known to modulate lymphocyte:endothelial interactions in vivo and in vitro (IFNγ, TGFβ, TNFα, IL-6, IL-1). In some experiments rats received, via portal venous infusion, a sterile inoculum of 150 × 10 6 semi-allogeneic (LBN F 1) spleen cells immediately or 12 h after the start of the study. In animals which were unchallenged with cells via the portal vein, subtle differences in detectable cytokines were observed between hepatic and portal blood samples, as reported in earlier studies. Within 12 h the minor perturbations observed in cytokine profiles following surgical insult resolved, and the changes between hepatic and portal venous samples remained constant throughout the study in control rats. However, in rats treated with LBNF 1 cells, changes in the cytokine profiles were seen compared with control animals, and as a function of time post F 1 cell infusion. Changes in mRNAs for different cytokines were observed in PBL taken from portal/hepatic blood in these same animals. These data point to one possible mechanism whereby the liver may influence immunological processes following portal venous antigen challenge.