Abstract
We have evaluated the effects of dexamethasone (Dex) alone or in combination with interleukin (IL)-10 or transforming growth factor-β1 (TGF-β1) on human T cell proliferation. Both IL-10 and TGF-β1 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-β1 was additive. IL-10, but not TGF-β1, 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-β1, but significantly less effective against the combination of Dex with IL-10. IL-10 and TGF-β1 are thus able to potentiate the Dex inhibitory effect on T cell proliferation and could be regarded as potential agents for future immunosuppressive protocols.
Footnotes
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Send reprint requests to: Mauro Brunetti, Laboratory of Immunopathology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy.
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↵1 Supported in part by grants from Ministero della Università e Ricerca Scientifica e Tecnologica (MURST) and from the “Eighth Research Project on AIDS,” Istituto Superiore di Sanità.
- Abbreviations:
- GC
- glucocorticoids
- TGF-β1
- transforming growth factor-β1
- IL
- interleukin
- APC
- antigen-presenting cells
- Dex
- dexamethasone
- PBMC
- peripheral blood mononuclear cells
- mAb
- monoclonal antibody
- PHA
- phytohemagglutinin
- r
- recombinant
- Received December 4, 1997.
- Accepted January 16, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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