Assessment of methotrexate as a potential immunosuppressive agent in baboons

Autor: David K. C. Cooper, K Teranishi, Leo Buhler, Michel Awwad, Sara Treter, Ian P. J. Alwayn
Rok vydání: 2001
Předmět:
Pulmonary and Respiratory Medicine
Xenotransplantation
medicine.medical_treatment
T-Lymphocytes
Administration
Oral
Extracorporeal immunoadsorption
Pharmacology
Disaccharides
Injections
Intramuscular
T-Lymphocytes/drug effects
Pharmacokinetics
Immunity
Transplantation Immunology
biology.animal
medicine
Animals
Methotrexate/pharmacokinetics/pharmacology
Transplantation
B-Lymphocytes
ddc:617
biology
Dose-Response Relationship
Drug
Immunosuppressive Agents/pharmacology
business.industry
Transplantation Immunology/drug effects
Mixed lymphocyte reaction
Antibody Formation/drug effects
Disaccharides/immunology
Methotrexate
B-Lymphocytes/drug effects
Antibody Formation
biology.protein
Surgery
Antibody
Lymphocyte Culture Test
Mixed
Cardiology and Cardiovascular Medicine
business
Immunosuppressive Agents
Baboon
medicine.drug
Papio
Zdroj: Journal of Heart and Lung Transplantation, Vol. 20, No 12 (2001) pp. 1335-9
ISSN: 1053-2498
Popis: 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.
Databáze: OpenAIRE
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