Pharmacodynamic modeling of lymphocytopenia and whole blood lymphocyte cultures in prednisolone-treated individuals. 1990

E Bloemena, and R P Koopmans, and S Weinreich, and C J van Boxtel, and P T Schellekens
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, Amsterdam.

In this study, we describe the time course of the influence of a single oral dose of prednisolone (10 mg) in man on the proliferative response of peripheral blood lymphocytes in whole blood. The data were fitted to an integrated pharmacokinetic-pharmacodynamic model, relating the plasma concentrations of prednisolone to its effect. The determination of prednisolone-induced lymphocytopenia and monocytopenia in vivo and the assessment of the influence of varying lymphocyte and monocyte numbers on proliferative responses in vitro enabled us to calculate the relative contributions of several prednisolone-induced effects to the diminished lymphoproliferative responses in whole blood after administration of prednisolone in vivo. We demonstrate that the decrease of the proliferative response in whole blood lymphocyte cultures stimulated with a monoclonal antibody directed against CD3 is mainly determined by the time course of the prednisolone-induced lymphocytopenia. The time course of the monocytopenia and the relative changes in the CD4+ and CD8+ T-cell subpopulations induced by prednisolone and the direct inhibitory effect of the changing plasma concentrations of the drug also contribute to the decrease of aCD3-stimulated whole blood lymphocyte cultures to some extent. The decrease of the proliferative response in whole blood lymphocyte cultures stimulated with a horse anti-human lymphocyte serum closely followed the time course of the lymphocytopenia induced by prednisolone. However, this response remained decreased for a longer period of time than could be expected on the basis of the prednisolone-induced lymphocytopenia in vivo. A possible mechanism which might explain this discrepancy between the prednisolone-induced effects in vivo and in vitro will be discussed.

UI MeSH Term Description Entries
D007165 Immunosuppression Therapy Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. Antirejection Therapy,Immunosuppression,Immunosuppressive Therapy,Anti-Rejection Therapy,Therapy, Anti-Rejection,Therapy, Antirejection,Anti Rejection Therapy,Anti-Rejection Therapies,Antirejection Therapies,Immunosuppression Therapies,Immunosuppressions,Immunosuppressive Therapies,Therapies, Immunosuppression,Therapies, Immunosuppressive,Therapy, Immunosuppression,Therapy, Immunosuppressive
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D007959 Lymphocyte Culture Test, Mixed Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens. Leukocyte Culture Test, Mixed,Mixed Lymphocyte Culture Test,Mixed Lymphocyte Reaction,Mixed Leukocyte Culture Test,Mixed Leukocyte Reaction,Leukocyte Reaction, Mixed,Leukocyte Reactions, Mixed,Lymphocyte Reaction, Mixed,Lymphocyte Reactions, Mixed,Mixed Leukocyte Reactions,Mixed Lymphocyte Reactions
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
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
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008231 Lymphopenia Reduction in the number of lymphocytes. Lymphocytopenia,Lymphocytopenias,Lymphopenias
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D011239 Prednisolone A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. Di-Adreson-F,Predate,Predonine,Di Adreson F,DiAdresonF

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