Effects of tacrolimus and dexamethasone on tubulointerstitial fibrosis in mercuric chloride treated Brown Norway rats.

We investigated the effects of daily injection of tacrolimus (FK), an immunosuppressor, or dexamethasone (Dx), an antiinflammatory agent, on renal tubulointerstitial fibrosis in mercuric chloride-treated Brown Norway rats. The tubular lesions observed after one time injection of mercuric chloride were reduced in FK-treatment group, but not in Dx-treatment group. Moreover, FK reduced infiltration of mononuclear cells, especially macrophages, and proliferation of myofibroblasts in renal intestitium and also inhibited renal interstitial fibrosis through the reduction of the expressions of fibrosis-related factors, i.e. plasminogen activator inhibitor-1 and transforming growth factor-beta1. On the other hand, Dx reduced lymphocyte infiltraton, but did not inhibit macrophage infiltration. In addition, Dx did not suppress myofibroblast profiferation, upregulation of fibrosis-related factors, and interstitial fibrosis. From these findings, it is suggested that FK may inhibit renal interstitial fibrosis through inhibition of macrophage infiltration, and that macrophages and myofibroblasts are very important fibrogenic factors in the development of mercuric chloride-induced renal tubulointerstitial fibrosis in BN rats.