抄録
Objective: Administration of mercuric chloride (HgCl2) to Brown Norway (BN) rats causes autoimmune glomerulonephritis and necrotizing vasculitis in the gut. In this study we analyzed the effects of FK506 on tissue injury and autoantibody production in HgCl2-treated BN rats.
Methods: FK506 was administered during the“early phase” (days 1 to 10, concurrently with HgCl2) or the“late phase” (days 11 to 14) . The autoantibody titers and urinary protein levels were mesured serially during the experimental period. Histopathological grade of tissue injury was assessed after the rats were sacrificed on day 15.
Results: HgCl2-treated BN rats showed interstitial pneumonitis in the lung, necrotizing vasculitis in the gut and glomerulonephritis. The titers of anti MPO and anti DNA antibodies increased to a maximum on day 10. FK506 given during the early phase significantly inhibited autoantibody increases, pneumonitis and proteinuria. On the other hand, FK506 given during the late phase exacerbated the vasculitis in the gut but slightly lowered the titer of anti MPO antibodies.
Conclusion: These results indicate that the effect of FK506 depends on the time of administration, or the pathological state at the time of treatment. Early administration of FK506 as a combination treatment may prevent necrotizing vasculitis caused by immunological mechanisms.
