The role of IL-13 in IgE synthesis by allergic asthma patients

Abstract

SUMMARYIgE 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 contribute to the production of IgE in allergic patients. To address this question we used an in vitro culture system in which the production of IgE is dependent on endogenously produced IL-4 and IL-13. In cultures of purified T and B cells from allergic asthma patients and non-atopic controls, T cells were polyclonally stimulated to obtain IL-4, IL-13 and subsequently IgE secretion. The absolute amount of IgE produced was not significantly different between patients and controls. When neutralizing IL-4 antibodies were included during culture, the production of IgE was dramatically inhibited in both patients and controls (production of IgE was reduced to 12%). However, neutralization of IL-13 led to a significantly stronger inhibition of IgE production in the patient group: production of IgE was reduced to 23 Ϯ 3% versus 50 Ϯ 10% in the control group. Corresponding with these results, we also observed a higher production of IL-13 by the patients, while the production of IL-4 was not significantly different. A more detailed analysis of the production of IL-13 revealed that patients' T cells were less sensitive to a negative signal controlling IL-13 production. Our results indicate that, at least in vitro, IgE production in allergic asthma patients is more dependent on IL-13 than in non-atopics, due to enhanced IL-13 production and to enhanced IgE production in response to IL-13.

IL-13 Overexpression Predisposes to Anaphylaxis Following Antigen Sensitization

“…Furthermore, IL-13 expression and IL-13 gene polymorphisms have been found to associate with increased IgE expression in atopic patients (5,28). A direct role for IL-13 in regulating lung epithelial cell function has also been reported, indicating that IL-13 may differentially modulate subsets of lung fibroblasts, inducing recruitment and activation of inflammatory cells (29).…”

“…Genetic and immunological analyses of atopic individuals have revealed that Th2-type cytokines are causally associated with atopy (2,4). Recently, elevated levels of IL-13 have been found to correlate with IgE and atopy in allergic asthma patients (5), and a search for genetic variants of the IL-13 gene and its signaling components has emphasized an important role for this cytokine in asthma and atopy (6). Experimental mouse models have also highlighted the importance of IL-13 in immune responses and atopy.…”

Opuntia humifusamodulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model

“…In asthma, Th2-related cytokines such as IL-4 [35–37], IL-5 [38], and IL-13 [35,37] significantly increase; the development of antibodies against Th2-related cytokines is an active field of research [39]. Changes in Th17 cells correlate with asthma induction, making it important to analyze Th-17 proteins such as TNF-α, IL-6, and IL-1β [40].…”

Prostanoids modulate inflammation and alloimmune responses during graft rejection

“…In macrophages, PGE2 down-regulates the expression of MHC class II antigens (10), inhibits the production of IL-1 (11), IL-12 (12,13), TNF-α (14), and superoxide (15) and increases IL-10 production in response to LPS (12,16). This pattern of cytokine release by APCs favors the differentiation of naive T cells towards a Th2 phenotype and promotes B lymphocyte isotype switching to IgE.…”