Demonstration of the therapeutic potential of non-anaphylactogenic anti-IgE antibodies in murine models of skin reaction, lung function and inflammation.
BACKGROUND
Allergies and allergic asthma are believed to be mediated by allergen-specific IgE antibodies. We have investigated the therapeutic potential of inhibiting endogenous IgE by a non-anaphylactogenic anti-mouse IgE antibody 1-5 with respect to its effects on antigen-induced skin reaction, lung function changes and lung inflammation in mice.


METHODS
Mice were immunized with benzylpenicillinoyl-KLH or ovalbumin, and antigen-mediated skin reaction, bronchoconstriction, bronchopulmonary hyperresponsiveness (BHR) and lung eosinophilic inflammation determined in anti-IgE 1-5-treated versus untreated animals.


RESULTS
Application of anti-IgE 1-5 inhibited (by 90%) the serum IgE and, 3-4 days after onset of treatment, blocked the antigen-induced skin reaction. Furthermore, the antibody also inhibited (by 90%) the antigen-induced infiltration of eosinophils into the lung. This latter effect seems to be mediated by blocking the IgE-CD23 interaction and indicates that lung eosinophilic inflammation also depends on IgE. Moreover, when applied to rats passively sensitized with mouse IgE, antibody 1-5 inhibited the antigen-induced bronchoconstriction. A similar effect could be seen in actively immunized mice, where antibody 1-5 was able to inhibit (by 70%) the ovalbumin-induced bronchoconstriction as well as BHR.


CONCLUSIONS
In summary, non-anaphylactogenic anti-IgE antibodies can markedly inhibit IgE levels and IgE-mediated allergic reactions. Since bronchoconstriction, BHR and lung eosinophilic inflammation can be suppressed, such antibodies may be attractive principles for the treatment of allergic asthma.
Heusser
C H
CH
Asthma Allergy Research Department, Ciba Geigy Ltd., Basel, Switzerland.
Wagner
K
K
Bews
J P
JP
Coyle
A
A
Bertrand
C
C
Einsle
K
K
Kips
J
J
Eum
S Y
SY
Lefort
J
J
Vargaftig
B B
BB
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D016084:Bronchoconstriction; D004804:Eosinophils / Q000502:physiology; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017455:Receptors, IgE / Q000502:physiology; D012867:Skin / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D007073:Immunoglobulin E