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).