Nerve growth factor or IL-3 induces more IL-13 production from basophils of allergic subjects than from basophils of nonallergic subjects

Background: Studies show that nerve growth factor (NGF) exhibits immunomodu latory activity. This neurotrophin is found at high levels in the serum of asthmatic individuals, is released during allergic reactions, and is report ed to augment in vitro histamine and leukotriene C4 release by human basoph ils. Objective: Because basophils represent a substantial source of IL-4 and IL- 13, we tested the effects or NGF on the secretion of these cytokines by cel ls prepared from allergic subjects and cells prepared from nonallergic subj ects. Methods. Cytokine and histamine were measured in culture supernatants by EL ISA and fluorimetry, respectively. Both real-time RT-PCR and conventional R T-PCR were used to measure IL-13 mRNA expression. NGF receptor expression w as determined by 2-color flow cytometry. Results: Basopbil suspensions from allergic subjects secreted some 2.5-fold greater levels of IL-13 when cultured with NGF than did cells prepared fro m normal control subjects. Flow cytometry revealed no significant differenc es in TrkA receptors on basophils to explain these findings. The levels of IL-13 secreted by the 2 groups of donors also differed when cells were acti vated with IL-3 but not when they were activated with anti-IgE antibody. Bo th NGF and IL-3 failed to induce IL-13 in cell cultures depleted of basophi ls, suggesting that the measurable IL-13 was indeed basophil-derived. Real- time RT-PCR showed an average induction of IL-13 message above medium contr ol that was 4.3 (+/- 1.7)-fold with NGF and 8.9 (+/- 3.7)-fold with IL-3. F inally, NGF priming resulted in a remarkable enhancement of IL-13 induced b y anti-IgE. This was significantly greater than the priming observed for ei ther the IL-4 or histamine when this stimulus was used. Conclusion: NGF (like IL-3) can both directly stimulate IL-13 secretion and modulate IgE-mediated responses in basophils. Its enhanced effect on cells from allergic individuals raises the importance of this cytokine in the pa thogenesis of allergic disease.