In vitro IgE production by interleukin 4-stimulated human peripheral blood mononuclear cells is suppressed by rapamycin.
Rapamycin (RAPA) is a new immunosuppressant which is 50-fold to 100-fold more potent than cyclosporin A (CyA) in inhibiting cellular immune responses and allograft rejection in animal models of organ transplantation. The drug's effect on in vitro IgE synthesis by interleukin (IL)4-stimulated human peripheral blood mononuclear cells was examined and compared with CyA's effect in this study. RAPA was found to be about 100-fold more potent than CyA in inhibiting IgE synthesis. Its inhibitory effect on IgE production was significant if it was added to the culture before Day 6 of a 14-day culture. The suppression was accompanied by the inhibitory effect on cell proliferation and on IgE-binding factor (IgE-BF) production. IL2 was able to partially reverse CyA- but not RAPA-induced inhibition of IgE production. Commercial B cell growth factor (cBCGF) was not able to reverse either RAPA- or CyA-induced suppression of IgE synthesis. The strong inhibitory effect of RAPA in IgE synthesis may be useful in certain clinical applications where overproduction of pathogenic IgE is a key issue. RAPA can also be used as a tool to dissect the regulation of IgE production.
Laboratory of Nephrology, Notre-Dame Hospital Research Center, University of Montreal, Quebec, Canada.
H Y
HY
Luo
H F
HF
Chen
P
P
Daloze
J
J
Chang
G
G
St-Louis
J P
JP
Wu
D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology*; D020123:Sirolimus
D007376:Interleukin-2; D011090:Polyenes; D015847:Interleukin-4; D007073:Immunoglobulin E; D016572:Cyclosporine; D020123:Sirolimus