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

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Abstract

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 μg 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 KLH 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 alone could also be detected. Subjects who received DEPs and KLH had significantly increased IL-4, but not IFN-γ, 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. (J Allergy Clin Immunol 1999;1183-8.)

Section snippets

Subjects

Twenty-five healthy nonsmoking volunteers (11 men and 14 women), ranging in age from 21 to 55 years, were recruited in Los Angeles, California. Atopic subjects were chosen as individuals who might, under appropriate circumstances, mount an IgE response to a foreign protein when exposed through the airway. All subjects had a positive skin prick test response to at least one aeroallergen but not to dust mite allergens. Additionally, all subjects had a history of prior seasonal airway allergies

Mucosal Ig response to KLH alone

Initially it was necessary to establish an intranasal KLH immunization regimen that would elicit a local humoral immune response. Fig 1 shows the mucosal antibody response to KLH in 10 atopic subjects after 3 intranasal administrations with the antigen alone.

. Appearance of antibodies to KLH in nasal fluid samples after nasal immunization with KLH. Subjects were immunized on day 0, 14, and 28, and the levels of anti-KLH IgE, IgG, IgA, and IgG4 were measured (see “Methods” section). Units are

DISCUSSION

DEPs, as environmental pollutants, have become the focus of intense investigation as a model to elucidate the interaction between fossil fuel combustion products, the immune response, and disease outcomes.1, 12, 13 Studies in animal and human models have indicated that DEPs have mucosal adjuvant properties at the molecular and cellular level. In particular, the ability of DEPs to exacerbate allergic inflammation and augment production of allergic antibody has been demonstrated both in animal

Acknowledgements

We thank Dr Shigeru Takafuji (Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Tokyo, Japan) and Dr Hiroshi Takenaka (Department of Otorhinolaryngology, Kyoto Prefectural University of Medicine, Kyoto, Japan) for their kind gifts of diesel exhaust particles.

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    Supported by the UCLA Asthma, Allergy and Immunologic Disease Center (AI-34567 funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Environmental Health Sciences), USPHS Grant AI-15251.

    ☆☆

    Reprint requests: David Diaz-Sanchez, PhD, Division of Clinical Immunology/Allergy, Dept. of Medicine, 52-175 Center for Health Sciences, UCLA School of Medicine, Los Angeles, CA 90095-1680.

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