THE ROLE OF IL-13 IN IGE SYNTHESIS BY ALLERGIC-ASTHMA PATIENTS

IgE antibodies play a crucial role in allergic type I reactions. Only IL-4 and IL-13 are able to induce an immunoglobulin isotype switch to IgE in B cells. A major question is to what extent these cytokines con tribute to the production of IgE in allergic patients. To address this question we used an in vitro culture system in which the production o f IgE is dependent on endogenously produced IL-4 and IL-13. In culture s of purified T and B cells from allergic asthma patients and non-atop ic controls, T cells were polyclonally stimulated to obtain IL-4, IL-1 3 and subsequently IgE secretion. The absolute amount of IgE produced was not significantly different between patients and controls. When ne utralizing IL-4 antibodies were included during culture, the productio n of IgE was dramatically inhibited in both patients and controls (pro duction of IgE was reduced to 12%). However, neutralization of IL-13 l ed to a significantly stronger inhibition of IgE production in the pat ient group: production of IgE was reduced to 23 +/- 3% versus 50 +/- 1 0% in the control group. Corresponding with these results, we also obs erved a higher production of IL-13 by the patients, while the producti on of IL-4 was not significantly different. A more detailed analysis o f the production of IL-13 revealed that patients' T cells were less se nsitive to a negative signal controlling IL-13 production. Our results indicate that, at least in vitro, IgE production in allergic asthma p atients is more dependent on IL-13 than in non-atopics, due to enhance d IL-13 production and to enhanced IgE production in response to IL-13 .