EVIDENCE THAT RAPAMYCIN HAS DIFFERENTIAL-EFFECTS ON IL-4 FUNCTION - MULTIPLE IL-4 SIGNALING PATHWAYS AND IMPLICATIONS FOR IN-VIVO USE

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 ef fect of rapamycin on human IL-4, a cytokine controlling B and T cell f unction, show this not to be the case. Unexpectedly, rapamycin actuall y synergized with IL-4 in both the upregulation of CD23 expression and the downregulation of the type II (p75) TNF receptor, while in the sa me B cell line, rapamycin simultaneously inhibited the IL-4-dependent production of TNFalpha and beta. These results raise the possibility t hat multiple IL-4 signaling pathways may be responsible for the pleiot ropic effects of IL-4, and have important implications for both the ex perimental and possible clinical in vivo use of rapamycin as a selecti ve immunosuppressant.