The immunosuppressive effects of verapamil upon mitogen activated and allo-antigen inducible human cytotoxic T-lymphocytes.
In this study, the effect of verapamil, a phenylalkylamine-type Ca2+ antagonist, upon the activation of human mononuclear cells was investigated and a detailed analysis of the kinetics and dose related effects of verapamil upon alloreactive cytotoxic T-cells (CTL) was undertaken. Verapamil suppressed the release of interleukin-2, proliferation and generation of CTL activity in mitogen and alloantigen stimulated human T-lymphocytes in a dose related fashion. Verapamil suppressed the steady state levels of several T-cell activation-associated gene transcripts, i.e. the mRNA encoding for interleukin-2, and a cytotoxic T-cell specific serine esterase. Verapamil exerted a novel immune-suppressive effect, i.e. the inhibition of mature alloantigen-inducible cytolytic T-cells, thus rendering verapamil a progenitor of potent and clinically useful immunosuppressive drugs.
Zanker
B
B
Medizinische Klinik und Poliklinik, Johannes-Gutenberg Universität, Mainz, F.R.G.
Marx
S
S
Strom
T B
TB
Köhler
H
H
D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000097:blood; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007519:Isoantigens; D008934:Mitogens; D015375:Receptors, Interleukin-2; D014700:Verapamil