Combined inhibition effects of tacrolimus and methylprednisolone on in vitro human lymphocyte proliferation. 1995

M J Lee, and N Pyszczynski, and W J Jusko
Department of Pharmaceutics, State University of New York at Buffalo 14260, USA.

Tacrolimus (FK 506) has synergistic immunosuppressive effects in combination with corticosteroids. A steroid dose-lowering effect can be explained partly by the inhibition by FK 506 of cytochrome P-450 IIIA, which metabolizes corticosteroids. We investigated the influence of combinations of FK 506 and methylprednisolone (MPL) on the suppression of in vitro human lymphocyte proliferation. To quantify the type of drug interaction (synergistic, additive, and antagonistic), three methods (Drewinko's statistical analysis, median-effect principle, and normal distribution model) were used. The interaction appeared synergistic in most combination ratios, but the extent of synergism varied depending on the quantitative method. There may be optimal combination ratios of FK 506 and MPL which achieve more effective immunosuppressive effects.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008775 Methylprednisolone A PREDNISOLONE derivative with similar anti-inflammatory action. 6-Methylprednisolone,Medrol,Metipred,Urbason,6 Methylprednisolone
D010835 Phytohemagglutinins Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture. Kidney Bean Lectin,Kidney Bean Lectins,Lectins, Kidney Bean,Phaseolus vulgaris Lectin,Phaseolus vulgaris Lectins,Phytohemagglutinin,Hemagglutinins, Plant,Lectin, Kidney Bean,Lectin, Phaseolus vulgaris,Lectins, Phaseolus vulgaris,Plant Hemagglutinins
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016559 Tacrolimus A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Anhydrous Tacrolimus,FK-506,FK506,FR-900506,Prograf,Prograft,Tacrolimus Anhydrous,Anhydrous, Tacrolimus,FK 506,FR 900506,FR900506,Tacrolimus, Anhydrous

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