title: Rapamycin inhibits the in vitro release of soluble interleukin-2 receptor by activated peripheral blood mononuclear cells (PBMC) independently of the mode of activation.
abstract: In the present study we compared the effect of rapamycin to that of CsA on the in vitro responses of lectin (PHA), phorbol-ester (PMA) and CA2+ ionophore (ionomycin)-activated peripheral blood mononuclear cells by measuring the release of soluble IL-2R (sIL-2R), high levels of which have been detected in clinical syndromes characterized by an ongoing immune activation. PHA was the stimulant associated with high sIL-2R release, whereas ionomycin-induced sIL-2R release only exceeded the background response and the sensitivity of the ELISA kit. The highest sIL-2R release, however, was obtained when PMA was used in combination with either PHA or ionomycin. Rapamycin inhibited the release of sIL-2R in response to all activators, whereas CsA only abolished the ionomycin-induced sIL-2R release. In parallel experiments rapamycin inhibited cell proliferation in response to all stimulants with the exception of PMA/ionomycin, whereas CsA inhibited all proliferation. Our study clearly shows that for optimal sIL-2R release both Ca+ and protein kinase C-triggered signals are required and that rapamycin has a distinct advantage over CsA in inhibiting the release of sIL-2R, which has been shown to be a reliable marker of lymphocyte activation either in vivo or in vitro.
authors.affiliation: Molecular Immunopathology/Histocompatibility Laboratory, Onassis Cardiac Surgery Center, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Degiannis
authors.forename: N
authors.initials: N
authors.lastname: Hornung
mesh_terms: D001711:Biotransformation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011090:Polyenes / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D020123:Sirolimus
chemical_list: D007166:Immunosuppressive Agents; D007476:Ionophores; D010703:Phorbol Esters; D011090:Polyenes; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D016572:Cyclosporine; D020123:Sirolimus