Zusammenfassung
Die neue antilymphozytisch wirksame Substanz Cyclosporin A blockierte die Produktion und/oder Sekretion des Makrophagen-Migrations-Hemmfaktors (MIF) aus Concanavalin A-stimulierten humanen Lymphozyten. Eine einstündige Vorinkubation mit der Substanz, gefolgt von einer achtstündigen Inkubation der Zellen in Abwesenheit der Substanz, führte zu einer deutlichen Reduktion der MIF-Synthese, bzw. der Freisetzung von MIF. Die Vitalität der Zellen war nicht beeinträchtigt. Cyclosporin A interferierte nicht mit dem MIF-Effekt am Makrophagen. Wir schließen daraus, daß der molekulare Wirkungsmechanismus von Cyclosporin A, zumindest teilweise, auf der Blockierung der Synthese und/oder Freisetzung von Lymphokinen aus immunkompetenten Zellen beruht.
Summary
The new antilymphocytic agent Cyclosporin A was found to inhibit the production and/or secretion of migration inhibitory factor (MIF) in human lymphocytes stimulated by Concanavalin A. Preincubation for one hour with the compound, followed by 8 hr restoration period of the cells in absence of the drug, resulted in moderate decrease in MIF synthesis and/or release. Cell viability was not affected. The agent was shown not to interfere with MIF action on the macrophage. We conclude that the molecular mechanism of action of Cyclosporin A is based, at least partially, on a blockade of synthesis and/or secretion of lymphokines from immunocompetent cells.
Abbreviations
- MIF:
-
Macrophage migration inhibitory factor
- CS-A:
-
Cyclosporin A
- DTH:
-
Delayed-type hypersensitivity
- MEM:
-
Eagle's minimal essential medium
- Con A:
-
Concanavalin A
References
Bloom BR, Bennett B (1966) Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science 153:80–82
David JR (1966) Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA 56:72–77
Block LH, Jaksche H, Bamberger S, Ruhenstroth-Bauer G (1978) Human migration inhibitory factor: purification and immunochemical characterization. J Exp Med 147:541–553
Geczy CL, Friedrich W, Weck AL de (1975) Production and in vivo effect of antibodies against guinea pig lymphokines. Cell Immunol 19:65–77
Borel JF, Feurer C, Magnee C, Stähelin H (1977) Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology 32:1017–1025
Green CJ, Allison AC (1978) Extensive prolongation of rabbit kidney allograft survival after short-term cyclosporin A treatment. Lancet 1:1182–1183
Calne RY, Rolles K, White DJG, Smith DP, Herbertson BM (1978) Prolonged survival of pig orthotopic heart grafts treated with cyclosporin A. Lancet 1:1183–1185
Leoni P, Garcia RC, Allison AC (1978) Effects of cyclosporin A on human lymphocytes in culture. 1978. J Clin Lab Immunol 1:67–72
David JR, David RA (1970) In: Bloom BR, Glade PR (eds) In Vitro Methods in Cell-Mediated Immunity. Academic Press, New York, p 240
Tutschka PJ (1979) Cyclosporin A — A new outlook for immunosuppression in clinical transplantation Blut 39:81–87
David JR (1965) Suppression of delayed hypersensitivity in vitro by inhibition of protein synthesis. J Exp Med 122:1125–1133
Pick E, Manheimer S (1974) The mechanism of action of soluble lymphocytic mediators. Cell Immunol 11:30–46
Gershon RK (1974) In: Cooper MD, Warner NL (eds) Contemporary Topics in Immunology, Vol 3. Plenum Publishing, New York, p 1
Ramshaw IA, Bretscher PA, Parish CR Regulation of the immune response. I Suppression of delayed-type hypersensitivity by T cells from mice expressing humoral immunity. Eur J Immunol 6:674–679
Kaufmann SHE, Simon MM, Hahn H (1979) Specific Lyt 123T cells are involved in protection against Listeria monocytogenes and in delayed-type hypersensitivity to Listerial antigens. J Exp Med 150:1033
Mackaness GB, Lagrange PH, Miller TE, Ishibashi T (1974) Influence of dose and route of antigen injection on the immunological induction of T cells. J Exp Med 139:543–559
Gershon RK, Mokyr MD, Mitchell M (1974) Activation of suppressor T cells by tumor cells and specific antibody. Nature 250:594–596
Gershon RK, Orbach-Arbouys S, Calkins C (1974) Proc of the 2nd Intern Congress of Immunology. North Holland, Amsterdam, 123, p 2
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Block, L.H., Siegenthaler, W. & Drews, J. Inhibition of mitogen-induced lymphokine production by Cyclosporin A. Klin Wochenschr 58, 739–742 (1980). https://doi.org/10.1007/BF01478462
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DOI: https://doi.org/10.1007/BF01478462