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A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs

  • Published:
Biotherapy

Abstract

Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction, proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM; cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg, intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs every morning for serial 21 days. The blood concentrations of CsA, measured as trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at 5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of 0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from 0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL-2, PHA and Con-A, which were declined by CsA, were not affected by FK. In contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK decreased the proportion of OKIa1+ cells progressively during the course of treatment. Cytotoxic activity was suppressed by both CsA and FK. These results possibly indicate that CsA and FK exert their immunosuppressive effects via different mechanisms.

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Abbreviations

APC:

antigen presenting cells

BW:

body weight

CM:

complete culture medium

Con-A:

concanavalin-A

cpm:

counts per minute

CsA:

cyclosporin A

FK:

FK 506

GOT:

glutamate oxalacetic transaminase

GPT:

glutamate pyruvate transaminase

HBSS:

Hanks' balanced salt solution

IFN:

interferon

IL-2:

interleukin-2

LDH:

lactate dehydrogenase

MMC:

mitomycin C

MLR:

mixed lymphocyte reaction

NK:

natural killer

PBL:

peripheral blood lymphocytes

PHA:

phytohemag glutinin

PR:

proliferative responses

rIL-2:

recombinant interleukin-2

SI:

stimulation index

3H-TdR:

tritiated thymidine

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Authors and Affiliations

  1. The First Department of Surgery, Kyoto University Faculty of Medicine, 606, Kyoto, Japan

    Kyoichi Takaori, Yoshinori Nio, Kazutomo Inoue & Takayoshi Tobe

  2. The First Department of Pathology, Kyoto University Faculty of Medicine, 606, Kyoto, Japan

    Manaba Fukumoto

  3. The Department of Pharmacy, Kyoto University Faculty of Medicine, 606, Kyoto, Japan

    Tohru Hashida, Masato Yasuhara & Ryohei Hori

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  1. Kyoichi Takaori
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  2. Yoshinori Nio
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  4. Thein Tun
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Takaori, K., Nio, Y., Inoue, K. et al. A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on peripheral blood lymphocytes in dogs. Biotherapy 4, 129–137 (1992). https://doi.org/10.1007/BF02171757

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  • DOI: https://doi.org/10.1007/BF02171757

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