Control of in vivo IgE production in the mouse by interleukin 4.
In vitro studies have demonstrated that the cytokine IL-4 can, with the proper co-stimuli, induce IgE secretion. We have demonstrated in in vivo studies with a monoclonal anti-IL-4 antibody that this cytokine is required for the generation of the polyclonal primary IgE responses induced by injecting mice with GaM delta antibody or inoculating them with larvae of the nematode parasite Nippostrongylus brasiliensis (Nb), as well as for the secondary TNP-specific IgE response induced by immunizing mice with TNP-KLH on alum. We now report studies that demonstrate that: (1) the secondary polyclonal IgE response induced by repeated Nb inoculation, while mostly inhibitable by anti-IL-4 antibody, has an IL-4-independent component; (2) whereas treatment with anti-IL-4 antibody during a primary Nb inoculation does not prevent the rapid generation of a large IgE response during a second inoculation, treatment with anti-IL-4 antibody during both primary and secondary inoculation inhibits the development of a secondary IgE response by greater than 99%; (3) an established ongoing chronic IgE response, induced by inoculation of mice with larvae of the nematode parasite Heligmosomoides polygyrus (Hp), can be reduced by greater than 95% by administration of anti-IL-4 antibody; and (4) an anti-IL-4 receptor antibody effectively, efficiently and selectively blocks the GaM delta antibody-induced IgE response. These observations suggest that approaches aimed at blocking IL-4 effects may be useful for treating IgE-mediated diseases.
Finkelman
F D
FD
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Katona
I M
IM
Urban
J F
JF
Paul
W E
WE
D000818:Animals; D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007139:Immunoglobulin epsilon-Chains / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007139:Immunoglobulin epsilon-Chains; D015847:Interleukin-4