Toluene diisocyanate (TDI) is a widely used industrial chemical causing respiratory sensitization in some exposed individuals. In spite of intensive research, understanding of the mechanism of chemical allergy is unclear. B and T lymphocyte activation, T helper differentiation and tissue pathology, largely controlled by the release of cytokines, are required for an organism to mount an effective immune response. The pleitropic, potent pro-inflammatory cytokine TNF may contribute to the induction +/or illicitation phase of TDI sensitization. To address this hypothesis TNF RI/R2 -knockout mice (C57 black) were sensitized (sc, 20 microl, day 1) boosted (sc, 5 micro1, days 4, 11) and repeatedly challenged (inhal., 100 ppb, days 21, 23 and 25) with TDI (80:20, 2,4:2,6 TDI). TOI sensitized and challenged wild type mice were included in the study as positive controls. Twenty-four hours following the last inhalation challenge the mice were sacrificed and their blood was collected for analysis of total IgE and TDI-specific IgG and IgE. Lungs were collected for RT-PCR measurement of IL-4, IL-S and INF-y mRNA expression and histopathologic evaluation of the airways. Total IgE was significantly increased in the knock-out mice compared with the wild type controls. In contrast, the titers of TDI-specific IgG and IgE were reduced in the TNF R1/R2 mice. Histopathology indicated differences in the trachea, nasal area and formation of germinal centers of regional lymph nodes. Similar results were obtained in normal mice receiving TNF neutralizing antibody prior to TDI exposure. The results of this study suggest that the pro-inflammatory cytokine TNF participates in the murine, immune response to TDI including TDI-specific antibody production and class switching.
Toxicology; Toxins; Toxic-materials; Statistical-analysis; Analytical-methods; Analytical-chemistry; Chemical-analysis; Animal-studies; Laboratory-animals; Exposure-assessment; Airborne-particles; Particulates; Respiratory-system-disorders; Pulmonary-system-disorders; Allergic-disorders; Allergic-reactions; Allergies; Allergens
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana