Exogenous interleukin-6 enhances liver regeneration after major and extreme liver resection

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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS

reduced CsA promoted EBV- B cell colony formation to 22.5 ⫾1.76. CsA induced EBV-B cell 3H-thymidine uptake from control of 12, 481⫾670 to 26,514 ⫾2732 (CPM/well). Vit.E at 40␮M reduced CsA promoted 3H-thymidine uptake to 16,146 ⫾2088 (n⫽6, P⬍0.05). Conclusion: This observation provides evidence that CsA induced oxidative stress activates NF␬B and promotes EBV infected B cell transformation. These events could be blocked by antioxidant Vit.E. These findings add to the understanding of the mechanism of CsA promoted EBV related post-transplant lympho-proliferative disorders (PTLD). 436. EXOGENOUS INTERLEUKIN-6 ENHANCES LIVER REGENERATION AFTER MAJOR AND EXTREME LIVER RESECTION. X. Jin, T. A. Zimmers, E. A. Perez, L. G. Koniaris; University of Miami, Miami, FL. Objective: To determine the potential therapeutic benefits of exogenous administration of interleukin-6 (IL-6), hepatocyte growth factor (HGF) or the combination on the hepatic regenerative response in vivo. Methods: Mice were administered recombinant IL-6 alone (400ng/ul or 400ng/hr), HGF alone (400ng/ul or 400ng/hr) or the combination by osmotic mini-pump. Alternatively, mice were injected with cells over-expressing IL-6. Mice were subjected to no surgery, sham surgery, 70% or 90% hepatectomy. Results: Exogenous IL-6 by pump induced liver growth without fat or muscle wasting, resulting in high plasma IL-6 level (1471.6 ⫾ 149.4 pg/ml ) versus control (14.5 ⫾ 0.8pg/ml). IL-6 administration by either route increased both total and fractional liver mass and stimulated hepatocyte proliferation, as revealed by increased hepatic mitotic figures, BrdU incorporation and PCNA expression. In contrast, HGF alone did not increase liver mass or PCNA expression, while coadministration of HGF and IL-6 did not increase liver mass or PCNA expression over IL-6 alone. IL-6 also induced expression of the antiapoptotic factors Bcl-2 and Bcl-xL. IL-6 accelerated liver regeneration and recovery of liver mass, with earlier hepatocyte entry into S phase and decreased expression of pro-apoptotic factors, including caspase-3 and cleaved PARP after 70% hepatectomy. IL-6 also improved survival and accelerated liver growth after 90% hepatectomy. Conclusions: Exogenous IL-6, but not HGF, can induce liver growth in non-injured livers. Furthermore, IL-6 administration can enhance the hepatic regenerative response by increasing hepatocyte proliferation and reducing hepatocyte apoptosis. These findings suggest IL-6 therapy has the potential to enhance liver growth and regeneration in clinical settings.

allograft outcomes. Additionally, serum lipid metabolites (by HPLC) involved the in 3 major enzymatic pathways (cycloxygenase, lipoxygenase and Soluble epoxide hydrolase were also assessed and correlated with allograft outcome. Results and Discussions. RT-PCR data were divided into 4 groups based on post-transplant patient biopsy results: non-rejection (NR, n⫽30), acute rejection (AR, n⫽4), acute tubular necrosis (ATN, n⫽9) and chronic nephropathy (CN, n⫽4). Expression of most of the inflammatory and lipid metabolism genes was higher in AR patients when compared to NR (p⬍0.05) (Fig.1). Specifically, IL-6, TNF␣ and CCL3/MIP1,LDL, CCL2/MCP1, Cyclooxygenase 2 (COX2), Lipoxygenase 5 (ALOX5), PPAR␣, and HMG-CoA reducatase expression were increased 1.1 to 1.5 fold (p⬍0.05) in AR patients. Conversely, adipose expression of adiponectin and leptin were significantly decreased in AR patients when compared to NR (p⬍0.01). Serum concentrations of ecosanoids PGF2␣, PGD2 (p⬍0.01) and PGE2 (fig.2) were decreased in AR suggesting a possible protective role for cyclooxygenase. Serum levels of lipoxygenase and epoxide hydrolase metabolites were not significantly different between AR and NR groups. There were no significant correlations of age, gender, ethnicity, BMI, etiology of renal failure, and dialysis type and durations among study groups. Conclusion. Expression of pretransplant proinflammatory and lipid metabolite genes were increased in retroperitoneal adipose tissue in AR patients. Further study has been focusing on adipose tissue gene expression and its role in transplant immune response.

437. ASSOCIATION OF PRETRANSPLANT PROINFLAMMATORY ADIPOKINES AND RENAL ALLOGRAFT OUTCOME - A PILOT STUDY REPORT OF PRETRANSPLANT RETROPERITONEAL ADIPOSE TISSUE GENE EXPRESSION. Y. Lu 1, W. Craig 2, G. Espinal 2, B. Hammock 3, K. Schmelzer 3, C. Troppmann 1, J. McVicar 1, T. Weaver 1, R. Perez 1; 1University of California Davis Medical Center, Department of Surgery, Sacramento, CA, 2UC Davis, Departments of Pediatrics and NPB, Davis, CA, 3UC Davis, Department of Entomology and Analytical Biochemistry, Davis, CA. Introduction. It is clear that adipose tissue plays an important role in regulation of inflammation and immunity. The importance of immunomodulatory role of adipokines in transplantation has not been elucidated. In this pilot study, we investigated the hypothesis that the alteration of pre-transplant proinflammatory gene expression in retroperitoneal adipose tissue increases the risk of acute allograft rejection and inflammation of renal transplant recipients. Methods. Samples of 63 consecutive kidney transplant recipients were included in the study. Pretransplant retroperitoneal adipose tissue was obtained during surgery for gene expression analysis by real-time RT-PCR. A panel of 18 genes involved in the inflammatory response and lipid metabolism were examined and correlated with

438. HISTOPATHOLOGIC FINDINGS IN A MODIFIED HETEROTOPIC FEMORAL HEART TRANSPLANTATION