Open AccessFK506, a novel immunosuppressive agent, induces antigen‐specific immunotolerance in active Heymann's nephritis and in the autologous phase of Masugi nephritis
Author(s) -
OKUBO Y.,
TSUKADA Y.,
MAEZAWA A.,
ONO K.,
YANO S.,
NARUSE T.
Publication year - 1990
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1990.tb05470.x
Subject(s) - nephritis , antigen , immunology , medicine , immune system , antibody , immunosuppression , immunosuppressive drug , transplantation
SUMMARY FK506 is a new drug which has potent immunosuppressive activity. We studied its immunosuppressive effects on active Heymann's nephritis and the aulologous phase of Masugi nephritis. The induction of active Heymann's nephritis was completely suppressed by FK506 injected simultaneously with the antigen (day 1) and then daily for 14 days at a dose of 0.64 mg/kg per day or more. With a lower dosage of this agent, antibody production and immune deposits in the glomerular basement membrane occurred despite the suppression of proteinuria. Similar results were obtained in rats on other treatment schedules (1–7 days or day 8–14 days duration). Rats that were prevented from developing Heymann's nephritis or the autologous phase of nephrotoxic antiserum nephritis by FK506 treatment exhibited a suppressed immune response to a second immunization of the same antigen even 4 weeks after cessation of drug administration; however, they developed antibodies when inoculated with other antigens. Rat peripheral leucocyte counts and scrum creatinin were not remarkably influenced by the administration of FK506. These results indicate that FK506 has potent immunosuppressive activity, and it is suggested that it is able to induce an antigen‐specific immunotolerance.