Intestine as source of cytokines and growth factors.

BACKGROUND: The activation status of intestinal immune system cells is much higher than that of analogous peripheral cells. Increased serum concentrations of proinflammatory cytokines have been reported in various pathologic conditions; however, the source of these mediators has not been elucidated. OBJECTIVE: To assess the role of the human intestine and its lymphatic system in production of growth factors and proinflammatory cytokines. MATERIAL AND METHODS: Twenty liver transplant recipients and 20 donors were included in the study. Blood samples were obtained from the artery supplying the intestine, the portal vein, and a peripheral vein during liver harvesting in donors and after transplantation in recipients. An enzyme-linked immunosorbent assay was used to assess serum concentrations of IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and hepatocyte growth factor (HGF). RESULTS: In transplant recipients, IL-6 concentration in arterial blood was lower than that in portal blood (P < .049), whereas in donors, there was no significant difference in these concentrations. Neither recipients nor donors demonstrated significant differences in arterial or portal blood concentrations of TNF-alpha, TGF-beta, or HGF. CONCLUSIONS: In healthy human beings, the intestine is not a substantial source of IL-6, TNF-alpha, TGF-beta, or HGF. However, in patients with liver cirrhosis, the intestine is an important source of IL-6 but not of the other studied growth factors and cytokines.

Safety and efficacy of steroid-free immunosuppression with tacrolimus and daclizumab in liver transplant recipients: 6-year follow-up in a single center.

BACKGROUND: Avoidance of steroid therapy after solid-organ transplantation has become a major challenge. Corticosteroid (CS)-free maintenance immunosuppression not only eliminates the well-known adverse effects but also may improve long-term outcome. OBJECTIVE: To investigate whether a CS-free regimen of tacrolimus (Tac) in combination with daclizumab (Dac) induction therapy provides adequate coverage after orthotopic liver transplantation. PATIENTS AND METHODS: This 6-year, single-center, retrospective study included 25 liver transplant recipients randomized to a Tac/CS regimen (n = 18) vs a Tac/Dac regimen (n = 7) according to the protocol of the MASTER (Monoclonal Antibodies vs STERoids) Study. RESULTS: No significant difference was observed in patient and graft survival between treatment arms: 94.4% in the Tac/CS group vs 71.4% in the Tac/Dac group. The incidence of biopsy-proved acute rejection episodes was 23.5% in the Tac/CS group vs 14.3% in the Tac/Dac group (P = NS). Total duration of hospitalization did not differ significantly between groups: 46.5 days in the Tac/CS group vs 73.9 days in the Tac/Dac group. Liver function as estimated using serum alanine aminotransferase and aspartate aminotransferase activity and bilirubin concentration, was not significantly different between the groups during 5 years posttransplantation. However, after 6 years, alanine aminotransferase activity was significantly greater in the Tac/Dac group compared with the Tac/CS group. CONCLUSIONS: A CS-free regimen of Tac/Dac is as effective as Tac/Cs in achieving good patient and graft survival. However, no substantial benefits insofar as the safety of Tac/Dac therapy were evident during long-term follow-up.