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.

IL-13 Is a Key Regulatory Cytokine for Th2 Cell-Mediated Pulmonary Granuloma Formation and IgE Responses Induced bySchistosoma mansoniEggs

“…IL-4 has clearly been shown to be a key mediator of pulmonary granuloma formation, and parasite-induced IgE responses are believed to be almost entirely dependent upon IL-4 (18,47,59). Therefore, although IL-13 blockade does not directly inhibit IL-4 activity, it was possible that even modest effects on IL-4 production could explain the reduction in granuloma formation and IgE production in the sIL-13R␣2-Fc-treated mice.…”

“…While the role of IL-4 in regulating granuloma formation is still incompletely understood (6), IL-4 clearly plays a key role in IgE production (47), and most likely indirectly influences IL-5, and thus eosinophil differentiation through its role as a differentiation factor for CD4 ϩ Th2 cells (1). Thus, IL-13 blockade could indi-rectly affect granuloma formation and IgE production by downregulating IL-4 responses.…”

Immune sensing of food allergens promotes aversive behaviour

“…Because IL-4 is required for IgE production and the development of type 2 immune responses 25,26 , we next tested the role of IL-4 signalling through IL-4Ra in the induction of avoidance behaviour to OVA. We used a one-bottle assay for seven days to quantify the consumption of OVA solution when water was not provided.…”

The Role of Staphylococcus aureus and Its Toxins in the Pathogenesis of Allergic Asthma

“…The Th2 cytokines IL-4 and IL-13 promote the class switch of activated B cells to IgEproducing plasma cells [15,148,149]. IgE antibodies circulate in the blood and eventually bind to the high-affinity IgE receptor FcεRI expressed on the surface of, amongst other cells, mast cells.…”