Regulation of anaphylactic IgG1 antibody production by IL-4 and IL-10.
BACKGROUND
Different cytokines have been implicated in the regulation of isotype expression in primary and secondary antibody responses. The aim of this study was to assess the regulation of anaphylactic IgG1 and IgE antibodies by IL-4, IL-10 and IFN-gamma at different time points of the antibody response against PI, an immunosuppressive fraction of Ascaris suum extract, and ovalbumin (OVA).


METHODS
Wild-type or cytokine-deficient C57BL/6 or BALB/c mice were immunized with PI or OVA in different adjuvants. Twenty days later, they were boosted with the respective antigen. IgG1 and IgE antibodies produced during primary and secondary responses were measured by passive cutaneous anaphylaxis.


RESULTS
PI induced low levels of anaphylactic IgG1 antibodies in the primary response and moderate levels after the antigenic booster, which were IL-4-dependent. In the absence of IL-10 and IFN-gamma, PI-specific IgG1 and IgE enhanced significantly, indicating that these cytokines downregulated antibody production in primary and secondary responses. The IgG1 response to OVA in aluminium hydroxide or complete Freund's adjuvant was IL-4-dependent in the beginning of the primary response. Later on, it became only partially regulated by IL-4 in C57BL/6 mice and IL-4-independent in Th2-prone BALB/c mice. In contrast, IgE antibodies depended exclusively upon IL-4 during the entire time course.


CONCLUSIONS
These results indicate, first, that the IL-4 dependency of anaphylactic IgG1 antibody production, mainly in the secondary response, varies among mouse strains, and, second, that the nature of the antigen determines whether IL-10 and IFN-gamma limit the potential to make large amounts of anaphylactic IgG1 and IgE.
Silva
Aldacilene S
AS
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Cavalcante
Leuridan T
LT
Faquim-Mauro
Eliana L
EL
Macedo
Mahasti S
MS
D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D000947:Antigens, Helminth / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D007371:Interferon-gamma; D010047:Ovalbumin