Open AccessThe effect of cyclosporin A, FK506, and rapamycin on the murine chronic graft‐ versus ‐host response—an in vivo model of Th2‐like activity
Author(s) -
BUNDICK R. V.,
CRAGGS R. I.,
HOLNESS E.
Publication year - 1995
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.1365-2249.1995.tb05574.x
Subject(s) - immunology , in vivo , immunoglobulin e , sirolimus , immune system , medicine , calcineurin , immunopathology , biology , pharmacology , transplantation , antibody , microbiology and biotechnology
SUMMARY We have evaluated the effects of three potent immunosuppressive agents: cyclosporin A, FK506, and rapamycin, on a murine chronic graft‐versus‐host response (chronic GVHR). The chronic GVHR has previously been described lo be a Th2‐like response, and is characterized by a marked splenomegaly and hyper‐IgE production in the early stages of the response. The effects of the immunosuppressive agents on both splenomegaly and hyper‐IgE were measured 3 weeks after the induction of the chronic GVHR. Rapamycin was found to inhibit both splenomegaly and the hyper‐IgE response in a dose‐dependent manner. Unexpectedly cyclosporin A and FK506 were found to potentiate markedly both the splenomegaly and hyper‐IgE response at low doses before exhibiting an inhibitory effect at higher doses. We propose the differences of activity seen with rapamycin compared with cyclosporin A and FK506 may be explained by their different mechanisms of action, and also by the selectivity of low dose cyclosporin A and FK.506 for Th1 ‐like lymphocytes. The implications of these observations are discussed in relation to the use of these immunosuppressives for the treatment of Th2‐like diseases.