Anti-IL-4 antibody inhibits antigen specific IgE response but fails to prevent chicken gamma globulin-induced active systemic anaphylaxis: evidence for the involvement of IgG antibodies

ABSTRACT

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.