IL-4 is required to generate and sustain in vivo IgE responses.

Abstract

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.

• Authors: F D Finkelman, I M Katona, J F Urban Jr, J Holmes, J Ohara, A S Tung, J V Sample, W E Paul
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 141 Issue 7 Pg. 2335-41 (Oct 01 1988) ISSN: 0022-1767 [Print] United States
• PMID: 2459206 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Epitopes
• Histocompatibility Antigens Class II
• Immunosuppressive Agents
• Interleukins
• Interleukin-4
• Immunoglobulin E

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• B-Lymphocytes (immunology, metabolism)
• Epitopes (immunology)
• Female
• Histocompatibility Antigens Class II (analysis)
• Immunization, Secondary
• Immunoglobulin E (biosynthesis)
• Immunosuppressive Agents (administration & dosage)
• Interleukin-4
• Interleukins (immunology, physiology)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Nematode Infections (immunology)
• Nippostrongylus (immunology)