IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo

Transpl Immunol. 2004 Jun-Jul;13(1):43-53. doi: 10.1016/j.trim.2004.04.001.

Abstract

Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type 1 diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1beta, TNF-alpha and IFN-gamma. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or beta-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Line
  • Cytokines / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Graft Survival / drug effects*
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans Transplantation / immunology*
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation
  • bcl-X Protein

Substances

  • Bcl2l1 protein, mouse
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein
  • Interferon-gamma