Immunotoxicology of Inhaled Compounds—Assessing Risks of Local Immune Suppression and Hypersensitivity

Abstract

Immunotoxic risks associated with inhaled chemicals include (1) suppression of local defenses resulting in increased risk of pulmonary infection and (2) sensitization of the immune system resulting in respiratory hypersensitivity, including allergic asthma. Under laboratory conditions, environmentally relevant levels of many air pollutants enhance susceptibility to bacterial pneumonia in mice. Because these compounds do not necessarily affect systemic immune responses, conventional testing for immune suppression does not adequately predict this risk. The underlying mechanism is suppression of alveolar macrophage (AM) phagocytic activity that ordinarily clears these organisms from the lung. Hence, the most practical way to test for this risk is to assess AM function in bronchoalveolar lavage fluid. Methods for assessing chemicals for the potential to cause allergic asthma are not as clear-cut. Low-molecular-weight chemicals are not physically large enough to initiate an immune response on their own; to produce sensitization they must be reactive enough to complex with protein. Structure–activity approaches and testing in vitro for reactivity with protein have been proposed for use in hazard identification. Diisocyanates and acid anhydrides are structures associated with occupational asthma. These types of chemical allergen appear to be a subset of chemicals that test positive in contact sensitivity assays, such as the local lymph node assay (LLNA). It has been proposed that “asthmagens” can be further distinguished from other types of sensitizers by the potential to induce T helper 2-mediated responses. Several approaches have been proposed but none have been widely accepted.

This article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflects the views and policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Notes

This article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflects the views and policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.