Abstract
The immunosuppressive drug rapamycin, which inhibits the response of T cells to growth-promoting lymphokines, has been considered to act as a general inhibitor of cytokine action. Our investigations into the effect of rapamycin on human IL-4, a cytokine controlling B and T cell function, show this not to be the case. Unexpectedly, rapamycin actually synergized with IL-4 in both the upregulation of CD23 expression and the down-regulation of the type II (p75) TNF receptor, while in the same B cell line, rapamycin simultaneously inhibited the IL-4-dependent production of TNF alpha and beta. These results raise the possibility that multiple IL-4 signaling pathways may be responsible for the pleiotropic effects of IL-4, and have important implications for both the experimental and possible clinical in vivo use of rapamycin as a selective immunosuppressant.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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B-Lymphocytes / physiology
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Cell Division / drug effects
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Cells, Cultured
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Cyclosporine / pharmacology
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Humans
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Immunosuppressive Agents / pharmacology*
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Interleukin-4 / antagonists & inhibitors
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Interleukin-4 / physiology*
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Lymphocyte Activation / drug effects
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Lymphotoxin-alpha / metabolism
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Polyenes / pharmacology*
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Receptors, IgE / physiology
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Signal Transduction / drug effects*
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Signal Transduction / physiology*
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Sirolimus
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Stimulation, Chemical
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T-Lymphocytes / drug effects
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T-Lymphocytes / physiology
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Tacrolimus / pharmacology
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Tumor Necrosis Factor-alpha / metabolism
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Up-Regulation / drug effects
Substances
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Immunosuppressive Agents
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Lymphotoxin-alpha
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Polyenes
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Receptors, IgE
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Tumor Necrosis Factor-alpha
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Interleukin-4
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Cyclosporine
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Sirolimus
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Tacrolimus