Lack of association of antibodies with diisocyanate-induced airway inflammation, hyperreactivity and asthma.
Karol-MH; Matheson-JM; Lemus-R; Lange-RW; Luster-MI
Toxicologist 2001 Mar; 60(1):8
Diisocyanates are the most frequent cause of chemically-induced occupational asthma. Chemically-induced asthma differs from occupational asthma caused by high molecular weight allergens, in that specific antibodies are rarely found in the sera of patients with chemically-induced asthma. To investigate the role of anitbodies in the pathogenesis of the disease we used both animal and human data. Mice deficient in tumor necrosis factor (TNF) activity, i.e., TNF receptor knockout animals and animals pretreated with TNF neutralizing antisera were exposed to toluene diisocyanate (TDI). We have shown that these animals fail to develop sensitization to TDI as evidenced by the absense of both airway inflammation and hyperractivity following TDI exposure. C57BL/6J mice were sensitized by sc injection and challenged on 3 occasions by inhalation of the chemical. Blood was drawn and sera were evaluated for TDI-specific IgE and IgG as well as for IgG subclasses. Using ELISA, TDI-specific IgE was not detected. TDI-specific IgG antibodies, with titers ranging from 800 - 1200, were found in all TDI-exposed groups. Antibodies were present in animals pretreated with anti-TNF antiserum, and in TNFR knockout animals, although these animals had either greatly diminished or no evidence of TDI asthma. In human studies, sera from 200 automobile painters were evaluated for hexamethylene diisocyanate (HDI)-specific antibodies. Thirty % of the painters had specific IgG antibodies, 4% had specific IgE antibodies, and 4% had clinically diagnosed asthma but none of the latter asthmatics had specific IgE. These results indicate the lack of association of antibodies with symptoms of asthma in an animal model and in humans. The results imply that diisocyanate asthma occurs through an antibody-independent mechanism.
Allergens; Pathogenesis; Airway-obstruction; Animal-studies; Exposure-levels; Painters; Pulmonary-system-disorders; Respiratory-system-disorders; Laboratory-animals
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
Yale University, New Haven, Connecticut