Nasal challenge with diesel exhaust particles can induce sensitization to a neoallergen in the human mucosa

Background: Diesel exhaust particles (DEPs) increase in vivo IgE and cytokine production at the human upper respiratory mucosa, exacerbating allergic inflammation. Objective: We examined the ability of DEP exposure to lead to primary sensitization of humans by driving a de novo mucosal IgE response to a neoantigen, keyhole limpet hemocyanin (KLH), Methods: Ten atopic subjects were given an initial nasal immunization with 1 mg of KLH followed by 2 biweekly nasal challenges with 100 mu g of KLH. Identical nasal KLH immunization was then performed on 15 different atopic subjects, but DEPs were administered 24 hours before each KLH exposure. Results: Exposure to KLH alone led to the generation of an anti-KLH IgG and IgA humoral response, which was detected in nasal fluid samples. No anti-KLH IgE appeared in any subjects. In contrast, when challenged with MH preceded by DEPs, 9 of the 15 subjects produced anti-KLH-specific IgE. KLH-specific IgG and IgA at levels similar to that seen with KLH atone could also be detected. Subjects who received DEPs and KLH had significantly increased IL-4, but not IFN-gamma, levels in nasal lavage fluid, whereas these levels were unchanged in subjects receiving KLH alone. Conclusion: These studies demonstrate that DEPs can act as mucosal adjuvants to a de novo IgE response and may increase allergic sensitization.