Tacrolimus, but not cyclosporine A, significantly increases expression of ICAM-1 and IFN-gamma in the NOD mouse.
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.
Papaccio
G
G
Department of Experimental Medicine, Laboratory of Histology, School of Medicine, Second University of Naples, via L. Armanni 5, 80138 Naples, Italy. gianpaolo.papaccio@unina2.it
Latronico
M V
MV
Graziano
A
A
Lanza
A
A
Pedullà
M
M
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D016688:Mice, Inbred NOD; D008854:Microscopy, Electron; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016572:Cyclosporine; D016559:Tacrolimus