title: Immunosuppressive activity of 13-cis-retinoic acid in rats: aspects of pharmacokinetics and pharmacodynamics.
abstract: Pharmacokinetics and pharmacodynamics of 13-cis-retinoic acid (13-cRA) administered at doses that suppress experimental autoimmune encephalomyelitis (EAE) have been investigated in rats. Serum concentration of the drug measured following oral administration of 37 mg/kg/12 h reached a peak of 1.8 x 10(-5) M in 2 h and linearly declined to 7.8 x 10(-7) M at hour 12. When spleen cells (SC) collected from 13-cRA-administered animals were cultured in vitro, their proliferative response to the T-cell mitogen concanavalin A (ConA) was suppressed and this effect was dependent on in vivo serum concentrations of the drug. In addition, in vitro exposure of antigen-specific T-cell lines to 13-cRA concentrations equivalent to those observed in vivo caused a dose-dependent suppression of the proliferation induced by the antigen as well as by T-cell mitogens. On a molar basis, 13-cRA showed a stronger in vitro immunosuppressive activity than two immunosuppressive agents used in human therapy, cyclosporin A and 6-mercaptopurin.
authors.affiliation: Department of Neurological and Psychiatrical Sciences, University of Florence, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vergelli
authors.forename: J
authors.initials: J
authors.lastname: Olivotto
authors.forename: E
authors.initials: E
authors.lastname: Castigli
authors.forename: B
authors.initials: B
authors.lastname: Gran
authors.forename: L
authors.initials: L
authors.lastname: Raimondi
authors.forename: R
authors.initials: R
authors.lastname: Pirisino
authors.forename: L
authors.initials: L
authors.lastname: Amaducci
authors.forename: L
authors.initials: L
authors.lastname: Massacesi
mesh_terms: D000818:Animals; D000941:Antigens / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015474:Isotretinoin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000941:Antigens; D007166:Immunosuppressive Agents; D008934:Mitogens; D003208:Concanavalin A; D015474:Isotretinoin