Mechanism of pokeweed mitogen inhibition of rhIL-4-induced human IgE synthesis.
Pokeweed mitogen (PWM) suppressed rhIL-4-induced IgE synthesis in a concentration-dependent manner. When rhIL-4 was present from Day 0, PWM added to cultures on Day 0 or 3 inhibited MNC IgE synthesis but not when it was added on Day 6 or later. The concentration of interferon-gamma (IFN-gamma) in MNC culture supernatants varied directly with the quantity of PWM added. Conversely, rhIL-4-stimulated MNC culture IgE concentrations varied inversely with the dose of PWM added and the IFN-gamma concentrations induced. The addition of a rabbit polyclonal neutralizing anti-human IFN-gamma antibody to rhIL-4 plus PWM-stimulated cultures partially or completely reversed PWM-induced inhibition of rhIL-4-induced IgE synthesis. PWM failed to inhibit rhIL-4-induced IgE synthesis by isolated B cells cocultured with monocytes and T cells from a clone unable to produce IFN-gamma message or protein. These findings are consistent with the postulate that PWM inhibits rhIL-4-induced IgE synthesis by inducing the production of IFN-gamma.
Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina 27710.
J L
JL
Claassen
A D
AD
Levine
R H
RH
Buckley
D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D011043:Pokeweed Mitogens; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D011043:Pokeweed Mitogens; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma