Control of IgE responses. III. IL-6 and IFN-alpha are isotype-specific regulators of peak BPO-specific IgE antibody-forming cell responses in mice.
The ability of cytokines (IL-4, IL-5, IL-6, IFN-alpha, IFN-gamma, TNF-alpha, GmCSF) to regulate peak benzylpenicilloyl (BPO)-specific IgE antibody-forming cell (AFC) responses was investigated. These responses were induced in BALB/c mice by ip injection of BPO-keyhole limpet hemocyanin (BPO-KLH; 10 micrograms) in aluminum hydroxide gel on Days 0, 21, and 42. On Day 44, or on Days 43, 44, and 45, mice were injected sc with varying doses of cytokine or anti-cytokine antibody. On Day 46, the numbers of BPO-specific AFC (IgM, IgG1, IgE and IgA) in spleen were determined ex vivo in enzyme-linked immunosorbent spot assay. Among the cytokines tested, only IL-6 suppressed BPO-specific IgE AFC responses in an isotype-specific fashion (60-90%). However, treatment of mice with anti-IL-6 also suppressed these responses, suggesting that IL-6 can either suppress or increase peak antigen specific IgE responses, depending upon its concentration. Among the cytokines tested, only IFN-alpha increased BPO-specific IgE AFC responses in an isotype-specific fashion. Since treatment with anti-IFN-alpha suppressed these responses, it appears that IFN-alpha is required to maintain peak antigen-specific IgE AFC responses. IL-4 or IFN-gamma nonspecifically suppressed responses of all isotypes. Treatment with anti-IL-4 also suppressed IgE responses, suggesting that this cytokine is required to maintain peak antigen specific IgE responses. Treatment with anti-IFN-gamma increased IgE responses, indicating that IFN-gamma suppresses peak antigen-specific IgE responses.
Auci
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DL
Department of Pathology, State University of New York, Health Science Center, Brooklyn 11203.
Kleiner
G I
GI
Chice
S M
SM
Dukor
P
P
Durkin
H G
HG
D000818:Animals; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology*; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008198:Lymph Nodes / Q000502:physiology; D008297:Male; D008643:Mesentery; D051379:Mice; D010400:Penicillin G / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D007132:Immunoglobulin Isotypes; D015850:Interleukin-6; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010400:Penicillin G