Immunosuppressive activity of 13-cis-retinoic acid in rats: aspects of pharmacokinetics and pharmacodynamics
| Autor: | R Pirisino, Luca Massacesi, J. Olivotto, Bruno Gran, Laura Raimondi, Marco Vergelli, Luigi Amaducci, E. Castigli |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental medicine.medical_treatment T-Lymphocytes Guinea Pigs Pharmacology Lymphocyte Activation Pharmacokinetics Oral administration In vivo Cyclosporin a medicine Concanavalin A Animals Antigens Isotretinoin biology Dose-Response Relationship Drug Experimental autoimmune encephalomyelitis Immunosuppression medicine.disease In vitro Rats Rats Inbred Lew biology.protein Female Mitogens Immunosuppressive Agents |
| Zdroj: | Immunopharmacology. 37(2-3) |
| ISSN: | 0162-3109 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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