Interleukin-6 (IL-6) is an acute reactant cytokine with anti-thought to be the most important risk factor for postoperative inflammatory properties, which has been found to prevent complications in patients undergoing liver resection 1,2 and it injury in a model of acute hepatitis in mice through downregu-is an important cause of primary nonfunction of liver allolation of tumor necrosis factor alpha (TNF-a); to correlate grafts. [3][4][5] The potential mediators involved in WI/Rp injury inversely with markers of hepatocellular injury in patients are numerous, 6-8 and include acute phase reactant cytokines with liver ischemia; and to initiate liver regeneration in mice. and polymorphonuclear neutrophils (PMN). 3,9 Better underIn this study, we investigated the role of IL-6 in rodent models standing of the pathogenesis of WI/Rp injury of the liver and of hepatic warm ischemia/reperfusion (WI/Rp) injury. IL-6-the availability of an agent that could alleviate Rp injury deficient mice (0/0) were subjected to hepatic WI and com-would have important clinical implications. pared with C57BL/6 mice, as well as IL-6 0/0 mice pretreated Interleukin-6 (IL-6) is an acute phase reactant cytokine with recombinant IL-6 (rIL-6). The effects of rIL-6 following with pleiotropic biological effects. This cytokine plays a cenvarious periods of ischemia were further studied in models of tral role in hematopoiesis, host defense, and inflammation. 10 hepatic ischemia in rats. IL-6 0/0 mice had increased reperfu-IL-6 has been found to have potent anti-inflammatory propsion injury as assessed by transaminase levels and a tissue erties, particularly in preventing injuries related to endotoxenecrosis scoring system when compared with controls, an ef-mia. 11,12 In a rat model of endotoxin-induced tracheal injury, fect prevented by pretreatment with rIL-6. Similarly, rats pre-recombinant IL-6 (rIL-6) was found to significantly prevent treated with rIL-6 had reduced reperfusion injury and better neutrophil infiltration and reduce other markers of inflamsurvival than controls in each respective WI group. Tissue mation. 11 TNF-a expression measured by Northern blot analysis andAlthough the liver is an important source of IL-6 and the serum C-reactive protein (CRP) levels, a marker of inflamma-primary site for its clearance, 13 the role of IL-6 in liver disease tion, were significantly reduced in animals pretreated with is unclear. In an acute hepatitis model in mice, rIL-6 was rIL-6. Administration of antibodies to TNF-a reproduced the found to confer a high degree of hepatoprotection when given beneficial effect of rIL-6. Hepatocyte proliferation, as assessed before the induction of the injury. 14 This effect was thought by a scoring method for mitotic index and proliferating nuclear to be related to downregulation of tumor necrosis factor cell antigen staining, was markedly increased in rIL-6-treated alpha (TNF-a) production. In a recent prospective randomrats when compared with controls. In conclusion, this study ized study of hepatic vascular...

Activated human monocytes are a source of numerous beta-chemokines. The present study was conducted to determine whether these cells produce the human beta-chemokine I-309 and to compare the induction requirements of I-309 to those of other beta-chemokines. We demonstrate that appropriately stimulated adherence-purified human peripheral blood monocytes express I-309 transcripts and secreted I-309 protein. Two stimuli, immobilized IgG and lipopolysaccharide (LPS), synergize strongly to induce I-309 gene expression. We further demonstrate that the production of endogenous interleukin (IL)-1alpha plays a crucial role in I-309 induction. Thus, neutralization of endogenous IL-1alpha using an anti-IL-1alpha antiserum inhibits the induction of I-309 transcripts in response to stimulation with immobilized IgG and LPS, and exogenous IL-1alpha or IL-1beta induces I-309 transcripts in monocytes stimulated with immobilized IgG. Immobilized IgG and LPS have the opposite effect on monocyte chemoattractant protein-1 (MCP-1) gene expression, in that the induction observed with either stimulus alone is diminished using the two stimuli in combination. Furthermore, endogenous and exogenous IL-1 can be either stimulatory or inhibitory for MCP-1 gene expression depending on other signals delivered to the monocytes. Immobilized IgG and LPS synergize to induce macrophage inflammatory protein-1alpha transcripts, but endogenous IL-1 does not play a significant role. Thus, each of these beta-chemokine genes is under distinct regulatory control in human monocytes.