IL-6 mediated isotype specific suppression of hapten specific IgE in serum of BPO-KLH sensitized mice: role of IFN alpha in maintainance of hapten specific IgE responses.
The ability of IL-6 or IFN alpha or antibodies to these cytokines to regulate serum levels of hapten specific immunoglobulins (IgM, IgG1, IgE, IgA) was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten specific IgE antibody forming cell (AFC) response. To induce peak IgE responses, mice were injected intraperitonealy (i.p.) with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected s.c. with IL-6 (100-1000 U), IFN alpha (1000-10,000 U), anti-IL-6 (100-1000 neutralizing units [NU]), or anti-IFN alpha (1000-10,000 NU). On day 46, levels of BPO specific IgM, IgG1, IgE and IgA in serum were determined (ELISA). Data are expressed as micrograms/ml. IL-6 suppressed BPO specific IgE in serum in isotype specific fashion (to > 90%), increasing IgA (approximately 3 fold), and leaving IgM and IgG1 unchanged. Since removal of endogenous IL-6 with anti-IL-6 increased serum IgE, and suppressed IgG1 (approximately 50%), with IgM and IgA unchanged, this suggests that IL-6 is an isotype specific suppressor of peak IgE responses and as such may be useful in the therapeutic management of atopic disease. IFN alpha treatment increased serum IgE levels (60%), and potentiated IgA responses (> 30 fold), with IgM and IgG1 unchanged. Since removal of endogenous IFN alpha with anti-IFN alpha decreased IgE levels (approximately 50%), increasing IgA, with IgM and IgG1 unchanged, this suggests a role for IFN alpha as an isotype specific helper of peak IgE responses and in maintenance of IgA responses.
Auci
D L
DL
Department of Pathology, State University of New York Health Science Center at Brooklyn 11203.
Miller
H
H
Chice
S M
SM
Durkin
H G
HG
D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D044482:Benzeneacetamides; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010400:Penicillin G / Q000031:analogs & derivatives / Q000276:immunology
D044482:Benzeneacetamides; D006241:Haptens; D007132:Immunoglobulin Isotypes; D016898:Interferon-alpha; D015850:Interleukin-6; C015026:benzylpenicilloyl G; D007073:Immunoglobulin E; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D010400:Penicillin G