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

We studied the alterations of cytokines and ICAM-1 expression in the NOD mo use pancreas produced by the administration of Cyclosporine A (CY) and Tacr olimus (TA), two widely used immunosuppressive drugs. Results evidenced dif ferences in the effects of these two drugs. In fact, during treatment and a fter withdrawal, Ci-treated animals remained euglycemic, showed good islet cell preservation and had low levels of Th1 and Th2 cytokines; ICAM-positiv ity within the islets was also found to be relatively low. On the other han d, TA-treated animals had infiltrated islets containing numerous dendritic cells, adhesion molecule overexpression, increased IFN-gamma and ICAM-1 mRN A transcripts, and interestingly, high levels of circulating ICAM-1. Howeve r, even these animals remained euglycemic. These findings lead to the thoug ht that these drugs may exert their effects in very different ways. Moreove r, in TA-treated animals, the presence of an islet infiltrate containing nu merous dendritic cells coupled with maintenance of euglycemia is suggestive for the involvement of immunosurveillance mechanisms. (C) 2001 Wiley-Liss, Inc.