Endogenous interleukin 6 plays an obligatory role in interleukin 4-dependent human IgE synthesis.
The lymphokine interleukin (IL) 4 plays a crucial role in the regulation of IgE synthesis. In the present study, the cellular and cytokine requirements for the IL4-dependent induction of IgE synthesis in humans were analyzed. Recombinant IL4 could induce IgE synthesis by peripheral blood mononuclear cells and autologous T/B cell mixtures, but not by highly purified B cells. IgE induction by IL4 was strongly decreased in monocyte-depleted peripheral blood mononuclear cells. These results show that the induction of IgE synthesis by recombinant IL4 is T cell dependent and optimal in the presence of monocytes. IL5 and IL6, but not IL2, IL1 and tumor necrosis factor-alpha, strongly up-regulated the IL4-dependent synthesis of IgE, with modest effects on cell proliferation. An anti-IL6 polyclonal antibody strongly inhibited IL4-driven IgE production. Endogenous IL6 plays, therefore, an obligatory role in the IL4-dependent induction of IgE. However, a combination of IL4, IL5 and IL6 (with or without IL1) at optimal concentrations could not induce IgE synthesis by purified normal B cells, indicating that cytokine-mediated signals, although essential, are not sufficient for the IL4-dependent induction of IgE synthesis.
Vercelli
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D
Division of Immunology, Children's Hospital, Boston, MA 02115.
Jabara
H H
HH
Arai
K
K
Yokota
T
T
Geha
R S
RS
D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4; D015848:Interleukin-5; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology* / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E