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R2-TNO: The Role of Irritancy and Irritant-Induced Inflammation in the Elicitation of Respiratory Hypersensitivity Reactions

Principal Investigator

Dr.Ir. Josje Arts
TNO
Utrechtseweg 48
P.O. Box 360
NL - 3700 AJ Zeist
j.arts@voeding.tno.nl
Tel: +31 30 69 44 489
Fax: +31 30 69 60 264

Collaborators

Dr. Frieke Kuper - TNO Voeding
frieke.kuper@tno.nl
Dr. Nanne Bloksma - Utrecht Institute for Pharmaceutical Sciences, Utrecht University
m.a.bloksma@pharm.uu.nl

Description

A range of low molecular weight chemicals can cause adverse reactions in the airways such as allergic asthma, including occupational asthma. Allergies involve a generally symptom-free induction phase where sensitisation is induced, and an elicitation (challenge) phase, where inhalation of the chemical provokes respiratory reactions. Respiratory irritants can cause lung inflammation and asthma-like reactions in the absence of prior sensitisation, and may influence severity, duration and type of allergic reaction. This project investigated the role of irritation by sulfur dioxide (SO2) or silica in respiratory allergy induced by trimellitic anhydride. Surprisingly, irritation prior to challenge generally diminished the severity of the respiratory allergic reactions. The most likely explanation was the induction of protective epithelium by the irritant, which may have prevented or diminished contact of lung tissue to the subsequent exposure to the allergen.

Related Publications

JHE Arts, M Schijf, N Bloksma, CF Kuper, Respiratory allergy to trimellitic anhydride in the Brown Norway rat: the role of irritancy and irritant-induced inflammation by pre-exposure to amorphous silica, accepted for publication.

JHE Arts, N Bloksma, CF Kuper, Respiratory allergy to trimellitic anhydride in the Brown Norway rat: the role of irritancy and irritant-induced inflammation by pre-exposure to SO2, in preparation.

DL Valstar, MA Schijf, G Storm, JHE Arts, CF Kuper, N Bloksma, PAJ Henricks, Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma, Toxicology and Applied Pharmacology 2006, 211, 20-29.

DL Valstar, MA Schijf, FP Nijkamp, G Storm, JHE Arts, CF Kuper, N Bloksma, PAJ Henricks, Alveolar macrophages suppress non-specific inflammation caused by inhalation challenge with trimellitic anhydride conjugated to albumin, Archives of Toxicology 2006, 80, 561-571.

JHE Arts, N Bloksma, T Leusink-Muis, CF Kuper, Respiratory allergy and pulmonary irritation to trimellitic anhydride in Brown Norway rats, Toxicology and Applied Pharmacology 2003, 187, 38-49.

Timeline: January 2001 > July 2005

LRI funding: €231,865

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