Anti-IL-4 monoclonal antibody prevents antibiotics-induced active fatal anaphylaxis.
We previously reported that anti-IL-4 mAb (11B11) failed to prevent protein-induced fatal murine anaphylaxis. To investigate the effect of anti-IL-4 on hapten-induced anaphylaxis, a model of murine anaphylaxis induced by antibiotics, penicillin V (Pen V) and cephalothin (CET), was developed, and the effect of anti-IL-4 on the anaphylaxis was observed. Pen V and CET induced 100 and 70 to 90% fatal reactions, respectively, when C57BL/6 mice were sensitized i.p. with 500 microg of antibiotic-OVA conjugate with 2 x 10(9) Bordetella pertussis and 1.0 mg of alum and challenged i.v. with 100 microg of antibiotic-BSA conjugate 14 days later. Serum taken from mice sensitized to Pen V passively sensitized normal mice to develop systemic anaphylaxis, and this ability of the serum was abrogated by heating at 56 degrees C for 2 h or depletion of IgE, but not IgG, Abs. Thus, the antibiotic-induced fatal reaction was an IgE-dependent anaphylactic reaction. Administration of anti-IL-4 at the beginning of sensitization completely prevented the fatal anaphylactic reactions to both Pen V and CET. This effect of anti-IL-4 was associated with its suppressive activity on antibiotic-specific serum IgE, but not IgG, levels. More importantly, anti-IL-4 therapy in previously sensitized mice was also effective in preventing the fatal reactions and rapidly reduced the established IgE levels. This study provides a new animal model of hapten-induced anaphylaxis and indicates that blocking of IL-4 activity may be beneficial in allergic diseases caused by a variety of haptens in which IgE Abs play a major role.
Park
J S
JS
Department of Immunology, Institute for Medical Sciences, Chonbuk National University Medical School, Chonju, Republic of Korea.
Choi
I H
IH
Lee
D G
DG
Han
S S
SS
Ha
T Y
TY
Lee
J H
JH
Lee
W H
WH
Park
Y M
YM
Lee
H K
HK
D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D002512:Cephalothin / Q000276:immunology; D004342:Drug Hypersensitivity / Q000276:immunology*; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010404:Penicillin V / Q000276:immunology
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D002512:Cephalothin; D010404:Penicillin V