IL-12 regulation of parasite antigen-driven IgE production in human helminth infections.
Recombinant IL-12 inhibits IgE synthesis by IL-4-stimulated lymphocytes from healthy persons and influences the development of Th subset selection involved in Ig isotype selection. Whether endogenous IL-12 production modulates IgE synthesis in patients with elevated serum IgE is unknown. To examine this question we studied the effects of neutralizing anti-IL-12 or recombinant IL-12 on parasite Ag-driven polyclonal IgE production and corresponding IFN-gamma and IL-4 synthesis by PBMC from helminth-infected individuals. The addition of neutralizing anti-IL-12 Ab significantly inhibited parasite Ag-driven IgE production in 11 of 12 individuals (p < 0.001). Recombinant IL-12 (1-10 U/ml) suppressed Ag-driven IgE production in a dose-dependent fashion up to 94% relative to untreated cultures. The effect of endogenous IL-12 on IgE production occurred, in part, by suppressing Ag-induced IL-4 and augmenting IFN-gamma production. IL-12 did not suppress IgE synthesis by purified B cells. An IFN-gamma-independent effect of IL-12 on Ag-driven IgE production was suggested by the ability of human rIL-12 to suppress IgE synthesis in the presence of neutralizing anti-IFN-gamma. This study demonstrates that IL-12 modulates helminth Ag-driven IgE production, in part, by regulating the relative quantities of IFN-gamma and IL-4 generated by Ag-specific lymphocytes.
King
C L
CL
Division of Geographic Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Hakimi
J
J
Shata
M T
MT
Medhat
A
A
D000328:Adult; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000909:Antibodies, Helminth / Q000096:biosynthesis*; D000947:Antigens, Helminth / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005368:Filariasis / Q000276:immunology; D006373:Helminthiasis / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008117:Loa / Q000276:immunology; D008297:Male; D012552:Schistosomiasis / Q000276:immunology; D014957:Wuchereria / Q000276:immunology
D000906:Antibodies; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma