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Immunosuppressive properties of MX-68, a novel unpolyglutamatable antifolate.

Authors
  • Mihara, M
  • Suzuki, T
  • Kaneko, E
  • Takagi, N
  • Takeda, Y
Type
Published Article
Journal
Biological & pharmaceutical bulletin
Publication Date
Oct 01, 1997
Volume
20
Issue
10
Pages
1071–1075
Identifiers
PMID: 9353567
Source
Medline
License
Unknown

Abstract

MX-68 is a novel unpolyglutamatable antifolate. We here reported the in vitro and in vivo immunosuppressive properties of MX-68 compared with a polyglutamatable antifolate, methotrexate (MTX). MX-68 showed potent suppressive effects on mitogen-induced mouse splenic lymphocyte proliferation as well as immunoglobulin production from LPS-stimulated mouse splenic B cells. In in vivo studies, MX-68 significantly suppressed antigen-specific antibody production of both T cell-dependent antigen and T cell-independent antigen. Moreover, MX-68 inhibited a sheep red blood cell (SRBC)-induced delayed-type hypersensitivity (DTH) reaction by administration starting from the day of antigen immunization, but did not suppress the effector phase of the DTH reaction. MTX showed suppressive activities similar to MX-68 in all experiments. Interestingly, although MX-68 demonstrated somewhat stronger suppressive effects than MTX in vivo, the results from in vitro studies were reversed. These results suggest that polyglutamation is not always required to suppress immune responses and that MX-68 is a slightly stronger immunosuppressive drug than MTX in mice.

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