Portacaval shunt (Eck fistula) in dogs causes hepato- cyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this pro-cedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of he- patocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506’s efficacy for the treatment of chronic liver rejection. Also, the observa-tions support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cy-tosolic binding sites of FK506, repamycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.
|Number of pages||4|
|Publication status||Published - 1991|
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