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M9650293.TXT
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1996-03-09
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Document 0293
DOCN M9650293
TI Administration of IL-12 during ongoing immune responses fails to
permanently suppress and can even enhance the synthesis of
antigen-specific IgE.
DT 9605
AU Germann T; Guckes S; Bongartz M; Dlugonska H; Schmitt E; Kolbe L; Kolsch
E; Podlaski FJ; Gately MK; Rude E; Institut fur Immunologie, Mainz,
Germany.
SO Int Immunol. 1995 Oct;7(10):1649-57. Unique Identifier : AIDSLINE
MED/96128658
AB The synthesis of antibodies of the IgE isotype in mice largely depends
on IL-4, a cytokine that is released by T lymphocytes of the Th2
subtype. IL-12 is a cytokine considered to direct Th cell development
into a Th1 direction and to suppress Th2 responses including the
synthesis of IgE. Here we report about the influence of IL-12 on the IgE
responses of mice immunized with protein antigens adsorbed to aluminum
hydroxide. To avoid problems with the detection of IgE caused by an
excess of competitive IgG antibodies produced in IL-12-treated mice,
serum IgE was first extracted from the serum by plate-bound anti-IgE mAb
and then determined either as total IgE or as antigen-specific IgE by
using biotinylated anti-IgE or biotinylated antigen. Depending on the
strain of mice and the dose of IL-12 injected together with the antigen,
IL-12 can either temporarily suppress or augment the synthesis of
(antigen-specific) IgE antibodies. This applies for CBA/J mice immunized
six times in biweekly intervals with minute (0.1 micrograms/injection)
or three-times with large (5 micrograms/injection) amounts of the bee
venom allergen phospholipase A2 (PLA2). Under both conditions the
antibody response is characterized by the production of predominantly
IgG1 as well as IgE but very little IgG2a, IgG2b and IgG3 antibodies.
Simultaneous application of low doses of IL-12 (1 or 10 ng/day) led to a
2- to 4-fold enhancement of IgE production (PLA2-specific IgE or total
IgE). Only a high dose of 1 micrograms IL-12/day resulted in a 3- to
10-fold reduction of the IgE response. This suppression was not stable,
however, because the synthesis of IgE antibodies was stimulated to a
high level when these mice subsequently received a second course of
immunizations in the absence of IL-12. Likewise, the synthesis of IgE
was only temporarily suppressed by IL-12 treatment in CBA/J mice
immunized with keyhole limpet hemocyanin (KLH) as antigen. However,
application of low (10 ng/day) or high (1 microgram/day) doses of IL-12
during the primary course of immunizations of CBA/J mice with KLH
suppressed the IgE response slightly or strongly respectively. In
striking contrast, the KLH-specific IgE response of BALB/c mice was
upregulated even when high doses of IL-12 (1 microgram/day) were
injected simultaneously with the immunizations. Thus, these results
demonstrate a great variability regarding the influence of IL-12
treatment on ongoing IgE responses in vivo.
DE Animal Antibodies, Anti-Idiotypic/IMMUNOLOGY Antibodies,
Monoclonal/IMMUNOLOGY Antibody Specificity Hamsters
Hemocyanin/IMMUNOLOGY IgE/*BIOSYNTHESIS/IMMUNOLOGY IgG/BIOSYNTHESIS
Interleukin-12/ADMINISTRATION & DOSAGE/*PHARMACOLOGY Mice Mice, Inbred
BALB C Mice, Inbred CBA Phospholipases A/IMMUNOLOGY Rats Recombinant
Proteins/PHARMACOLOGY Support, Non-U.S. Gov't Th1 Cells/IMMUNOLOGY
Th2 Cells/*DRUG EFFECTS/IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).