It has recently been reported that
interleukin-4 (IL-4) is required for the production of
IgE, and anti-IL-4
monoclonal antibody (mAb) inhibits in vivo
IgE responses. These suggest that blocking of
IL-4 activity may be useful for the prevention or treatment of
immediate hypersensitivity disorders. In this study we investigated whether anti-IL-4 has a regulatory role in chicken-
gamma globulin (CGG)-induced active systemic
anaphylaxis. Multiple
injections of anti-IL-4 (up to 40 mg/mouse) failed to protect the mice from fatal
anaphylaxis. Anti-IL-4 strongly suppressed CGG-specific
IgE response (> 90%) without any suppressive effect on CGG-specific
IgG (
IgG1,
IgG2a,
IgG2b, and
IgG3) responses. Because these data suggest the possibility that fatal
anaphylaxis could be induced by
IgG antibodies, we examined the possibility using anti-CGG polyclonal and the subclasses of
IgG monoclonal antibodies. Passive sensitization of mice with polyclonal
antibodies elicited severe and fatal
anaphylactic shock; about 50% of the mice died. The activity of
antibodies was not diminished by heat treatment (56 degrees C, 2h), suggesting that the
anaphylaxis was not mediated by
IgE.
Shock was also elicited by each subclass of
IgG mAb; of these,
IgG1 was the most effective. Combination of the
IgG subclasses elicited more exaggerated
shock; about 30% of mice died. These data indicate that
IgG antibodies are themselves sufficient to induce systemic
anaphylaxis. Therefore, the failure of anti-IL-4 to prevent active
anaphylaxis is probably due to the inability of anti-IL-4 to suppress the production of
IgG antibodies.