IL-10 synergizes with dexamethasone in inhibiting human T cell proliferation.
We have evaluated the effects of dexamethasone (Dex) alone or in combination with interleukin (IL)-10 or transforming growth factor-beta 1 (TGF-beta 1) on human T cell proliferation. Both IL-10 and TGF-beta 1 significantly decreased the Dex concentration needed to inhibit T cell proliferation by 50% (IC50). Dex in combination with IL-10 completely inhibited T cell proliferation, even when IL-10 alone was ineffective, as in the case of phytohemagglutinin-induced T cell proliferation. The evaluation of the results according to the isobole method displayed a potent synergistic activity between Dex and IL-10, whereas the combination of Dex with TGF-beta 1 was additive. IL-10, but not TGF-beta 1, enhanced the inhibitory effect of Dex on IL-2 production. IL-2 and IL-4 only partly antagonized the antiproliferative effect of the combinations. IL-4 was as effective as IL-2 in antagonizing the combination of Dex with TGF-beta 1, but significantly less effective against the combination of Dex with IL-10. IL-10 and TGF-beta 1 are thus able to potentiate the Dex inhibitory effect on T cell proliferation and could be regarded as potential agents for future immunosuppressive protocols.
Brunetti
M
M
Department of Human Pathology, G. D'Annunzio University, Chieti, Italy.
Colasante
A
A
Mascetra
N
N
Piantelli
M
M
Musiani
P
P
Aiello
F B
FB
D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone