IL-4 is required to generate and sustain in vivo IgE responses.
Antibodies of the IgE isotype play a predominant role in immediate hypersensitivity reactions. IL-4, a T cell-derived lymphokine that stimulates increased Ia expression by resting B cells and increased IgG1 secretion by LPS-activated B cells in vitro, has also been shown to regulate in vitro and in vivo polyclonal IgE responses. We report that large quantities of a purified anti-IL-4 mAb inhibit primary in vivo polyclonal IgE responses by 99% in mice infected with Nippostrongylus brasiliensis or injected with anti-IgD antibodies, and totally inhibit secondary Ag-specific IgE responses to TNP-keyhole limpet hemocyanin without effect on either IgG1 or IgG2a responses to these stimuli. The lack of effect of anti-IL-4 antibody on IgG1 secretion cannot be explained simply by inadequate neutralization of IL-4, inasmuch as the doses of anti-IL-4 antibody used blocked an N. brasiliensis-induced increase in B cell Ia expression by more than 85%, whereas in vitro studies indicate that enhancement of B cell Ia expression requires less IL-4 than induction of IgG1 secretion. In addition to demonstrating that IL-4 plays a necessary role in the generation of an in vivo IgE response, we show that IL-4 has an important role in sustaining established IgE responses, because anti-IL-4 antibody, when given at the peak of an N. brasiliensis- or TNP-keyhole limpet hemocyanin-induced IgE response, accelerates the declines in total serum IgE and in IgE anti-TNP antibody levels, respectively. These observations suggest that the effects of IL-4 on in vivo immune responses may be more specific than might have been predicted from in vitro observations, and that regulation of IL-4 production or action may be useful for the prevention or therapy of immediate hypersensitivity disorders.
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
Holmes
J
J
Ohara
J
J
Tung
A S
AS
Sample
J V
JV
Paul
W E
WE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015847:Interleukin-4; D007378:Interleukins / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009349:Nematode Infections / Q000276:immunology; D009559:Nippostrongylus / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007378:Interleukins; D015847:Interleukin-4; D007073:Immunoglobulin E