Tacrolimus, but not cyclosporine A, significantly increases expression of ICAM-1 and IFN-gamma in the NOD mouse

J Cell Biochem Suppl. 2001:Suppl 36:107-16. doi: 10.1002/jcb.1092.

Abstract

We studied the alterations of cytokines and ICAM-1 expression in the NOD mouse pancreas produced by the administration of Cyclosporine A (CY) and Tacrolimus (TA), two widely used immunosuppressive drugs. Results evidenced differences in the effects of these two drugs. In fact, during treatment and after withdrawal, CY-treated animals remained euglycemic, showed good islet cell preservation and had low levels of Th1 and Th2 cytokines; ICAM-1 positivity within the islets was also found to be relatively low. On the other hand, TA-treated animals had infiltrated islets containing numerous dendritic cells, adhesion molecule overexpression, increased IFN-gamma and ICAM-1 mRNA transcripts, and interestingly, high levels of circulating ICAM-1. However, even these animals remained euglycemic. These findings lead to the thought that these drugs may exert their effects in very different ways. Moreover, in TA-treated animals, the presence of an islet infiltrate containing numerous dendritic cells coupled with maintenance of euglycemia is suggestive for the involvement of immunosurveillance mechanisms. J. Cell. Biochem. Suppl. 36: 107-116, 2001.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclosporine / pharmacology*
  • Female
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / ultrastructure
  • Mice
  • Mice, Inbred NOD
  • Microscopy, Electron
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / ultrastructure
  • RNA, Messenger / metabolism
  • Tacrolimus / pharmacology*

Substances

  • Immunosuppressive Agents
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma
  • Cyclosporine
  • Tacrolimus