Allergen immunotherapy decreases LPS-induced NF-κB activation in neutrophils from allergic patients.

ABSTRACT

BACKGROUND: Allergen-specific immunotherapy (IT) is widely used to treat allergic diseases. The molecular mechanisms have not been clarified yet completely. The present work was undertaken to analyze the effect of IT in the activation of NF-κB. METHODS: Neutrophils from 15 pollen-allergic IT-treated patients, 10 untreated pollen-allergic patients, and 10 healthy donors were in vitro stimulated with LPS. NF-κB activation (p65/p52) was measured in their nuclear extracts by enzyme-linked immunosorbent assay (ELISA). IκBα phosphorylation, NF-κB-repressing factor (NRF) activation, and thromboxane A2 (TXA2 ) and Interleukin-8 (IL-8) release were measured by ELISA. RESULTS: There was a positive correlation between the score of symptoms and NF-κB activation in human neutrophils. IT significantly decreased NF-κB activation levels in neutrophils compared with neutrophils from untreated patients. IκBα phosphorylation and NRF activation levels were, respectively, significantly lower and higher in neutrophils from IT-treated patients than from untreated patients. IL-8 and TXA2 release were significantly lower in neutrophils from IT-treated patients than from untreated patients. CONCLUSIONS: IT positive effects are at least in part mediated by the negative regulation of NF-κB activation in human neutrophils. These observations represent a novel view of neutrophils as possible cell target to treat IgE-dependent diseases through NF-κB downmodulation.