Dipyridamole in vitro suppresses the generation of T-cell cytotoxic functions: synergistic activity with cyclosporine.
The pharmacological activity of dipyridamole has been related to its ability to increase intracellular cAMP. Elevated cAMP concentrations can tone down T-cell effector functions. The aim of this study was to evaluate the dipyridamole effect in vitro on the generation of alloreactive cytotoxic and lymphokine-activated killer cells in normal T-cell subpopulations. Dipyridamole suppressed T-cell cytotoxic functions in a dose-dependent way. The kinetics of suppression showed that dipyridamole prevented the first step of cytotoxicity, i.e. activation of the lytic program following allogeneic or interleukin-2 stimulation. The ability of dipyridamole to interact with the immunosuppressive activity of cyclosporine was also investigated. By itself, cyclosporine suppressed the generation of alloreactive cytotoxicity, but not the generation of lymphokine-activated killer cells. A synergistic immunosuppressive activity between dipyridamole and cyclosporine was observed on the generation of alloreactive cytotoxic T lymphocytes.
Massaia
M
M
Dipartimento di Medicina ed Oncologia Sperimentale, Ospedale Molinette, Torino, Italy.
Bianchi
A
A
Attisano
C
C
Dianzani
U
U
Boccadoro
M
M
Pileri
A
A
D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D003524:Cyclosporins; D004176:Dipyridamole