title: Immunomodulating effects of the anti-viral agent Silibinin in liver transplant patients with HCV recurrence.
abstract: BACKGROUND
  Silibinin has been shown to have anti-HCV activity and immune-modulating properties by regulating dendritic cell (DC) function. DCs are antigen-presenting cells that, together with regulatory T cells (Treg), play a pivotal role in controlling alloimmune, as well as anti-HCV immune responses.
  
  
  METHODS
  Twelve liver transplant patients with HCV recurrence received iv infusion of Silibinin (iv-SIL) for 14 consecutive days. Using flow cytometry, before and at the end of treatment, we determined the frequencies of circulating myeloid (m) and plasmacytoid (p) DC and Treg and the expression of costimulatory/coregulatory molecules by the DC subsets and Treg. Statistical analysis was performed using the paired Student's t test and Pearson correlation test.
  
  
  RESULTS
  After iv-SIL treatment, we observed an elevated plasmacytoid dendritic cell (pDC)/myeloid dendritic cell (mDC) ratio, while pDC displayed lower HLA-DR and higher immunoglobulin-like transcript 4 (ILT4), CD39, and HLA-G expression compared to the pretreatment baseline. In addition, after iv-SIL, mDC showed increased inducible costimulator ligand (ICOSL) expression. No changes were detected in Treg frequency or programed death (PD)-1 expression by these cells. Moreover, several correlations between DC/Treg markers and clinical parameters were detected.
  
  
  CONCLUSIONS
  This descriptive study, in liver transplant patients with HCV recurrence, reveals the impact of iv-SIL on DC and Treg. The changes observed in circulating pDC and mDC that have previously been associated with tolerogenic conditions shed new light on how iv-SIL may regulate anti-viral and alloimmunity. We have also observed multiple clinical correlations that could improve the clinical management of liver transplant patients and that deserve further analysis.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
authors.forename: Antonino
authors.initials: A
authors.lastname: Castellaneta
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Massaro
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Rendina
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: D'Errico
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Carparelli
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261 USA.
authors.forename: Salvatore Fabio
authors.initials: SF
authors.lastname: Rizzi
authors.affiliation: Department of Emergency and Organ Transplantation, Unit of Gastroenterology, University Hospital, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy.
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.affiliation: Department of Emergency and Organ Transplantation, Unit of Gastroenterology, University Hospital, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
keywords: Dendritic cells; HCV recurrence; Liver transplantation; Regulatory T cells; Silibinin