title: Assessment of methotrexate as a potential immunosuppressive agent in baboons.
abstract: Methotrexate is an anti-proliferative agent that affects both T-cell and B-cell immunity, and therefore might be expected to suppress antibody (Ab) production. Although it has been used in xenotransplantation studies to suppress anti-pig Ab production, it has always been used in combination with other immunosuppressants. The purpose of this study was to measure its effect as a single immunosuppressant on anti-Gal Ab production in baboons (n=4). Pharmacokinetic studies showed that methotrexate was not detected in the blood when administered per os. Prolonged daily IV or IM administration (i) reduced T-cell and B-cell numbers by 50% to 70% and modestly reduced responsiveness on mixed lymphocyte reaction (but only at toxic doses) and (ii) did not result in lowered anti-Gal Ab levels, only marginally reducing the rate of return of Ab after extracorporeal immunoadsorption. Our observations would suggest that methotrexate will not contribute significantly to immunosuppressive regimens in the baboon at non-toxic doses.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02129, USA.
authors.forename: K
authors.initials: K
authors.lastname: Teranishi
authors.forename: S
authors.initials: S
authors.lastname: Treter
authors.forename: I P
authors.initials: IP
authors.lastname: Alwayn
authors.forename: L
authors.initials: L
authors.lastname: Buhler
authors.forename: M
authors.initials: M
authors.lastname: Awwad
authors.forename: D K
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects*; D004187:Disaccharides / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007273:Injections, Intramuscular; D007959:Lymphocyte Culture Test, Mixed; D008727:Methotrexate / Q000493:pharmacokinetics / Q000494:pharmacology*; D010215:Papio; D013601:T-Lymphocytes / Q000187:drug effects*; D014181:Transplantation Immunology / Q000187:drug effects*
chemical_list: D004187:Disaccharides; D007166:Immunosuppressive Agents; C055075:galactosyl-(1-3)galactose; D008727:Methotrexate