Evidence that rapamycin has differential effects of IL-4 function. Multiple IL-4 signaling pathways and implications for in vivo use

Transplantation. 1993 Aug;56(2):368-74. doi: 10.1097/00007890-199308000-00023.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology
  • Cell Division / drug effects
  • Cells, Cultured
  • Cyclosporine / pharmacology
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / physiology*
  • Lymphocyte Activation / drug effects
  • Lymphotoxin-alpha / metabolism
  • Polyenes / pharmacology*
  • Receptors, IgE / physiology
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology*
  • Sirolimus
  • Stimulation, Chemical
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology
  • Tacrolimus / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects


  • Immunosuppressive Agents
  • Lymphotoxin-alpha
  • Polyenes
  • Receptors, IgE
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Cyclosporine
  • Sirolimus
  • Tacrolimus