Pulmonary Immunotoxicity of Ozone: Alterations in Cytokine Metabolism and the Cell Mediated Immune Response

EPA Grant Number: R826410
Title: Pulmonary Immunotoxicity of Ozone: Alterations in Cytokine Metabolism and the Cell Mediated Immune Response
Investigators: Schlesinger, Richard B.
Institution: New York University Medical Center
EPA Project Officer: Hahn, Intaek
Project Period: April 7, 1998 through April 6, 2001 (Extended to April 6, 2002)
Project Amount: $410,026
RFA: Exploratory Research - Human Health (1997) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Human Health


The lungs are a target organ for environmental stressors in the form of air pollutants. Local pulmonary immune cell populations may be directly exposed to various airborne toxicants. Since these cells, such as pulmonary macrophages (PAM), play a pivotal role in host immunocompetence, their function may be compromised by pollutant exposure and this may be involved in the pathogenesis of environmentally-induced pulmonary disease. The objective of this study is to determine the effects of ozone on critical aspects of PAM activity involved in the induction of the cell-mediated immune (CMI) response. This concerns PAM interactions with cytokines, primarily the interferons (IFNa and IFNg), and the initiation of events associated with the early and late stages of PAM activation in response to a well-characterized CMI-specific human lung pathogen, Listeria monocytogenes. The hypothesis is that ozone-induced alterations in the ability of PAM to participate in the CMI response are mechanistically linked to changes in the capacity of these cells to form and later interact with immunoregulatory cytokines, primarily the interferons.


Both in vitro and in vivo exposure regimes will be employed. In vivo exposures will be for 4 hr/d, 5 d/wk, for 3 wk to ozone at 0.3 and 0.15 ppm. To be certain that PAM are the primary cells affected during the course of altered immune function, the effects of ozone upon T-lymphocytes, cells critical to PAM priming in the later stages of CMI response, will also be examined for possible changes in cytokine formation/binding. Using the well established Listeria host resistance model system to examine CMI function, ozone exposed rats will be analyzed for their resistance to and pulmonary clearance of a sublethal Listeria challenge. The critical role of ozone-induced altered PAM-IFN interactions in reduced CMI function will be illustrated by examining air-exposed rats rendered immunoincompetent at defined stages of the antilisteral response. In addition, cytokine release by PAM/T-cells at the early and late stages of resistance will be assessed, as will aspects of cytokine binding. Post-binding IFN metabolism by PAM will also be studied to clarify which IFN processing step might be predominantly affected by ozone. In order to measure the ultimate implication from altered PAM cytokine/IFN metabolism, ozone-induced changes in IFN/cytokine-inducible structural/functional endpoints will be examined.

Expected Results:

The effects of air pollutants upon the immune system is of concern as exposure to air pollutants has been implicated in the production of human health effects which may have as part of their pathogenesis immune system dysfunction. Without a better appreciation of basic mechanisms, accurate assessment of the immunotoxicity of ozone is not possible. Such information is a critical component of environmental health risk assessment processes for this criteria pollutant.

Journal Articles : 1 Displayed | Download in RIS Format

Other project views: All 1 publications 1 publications in selected types All 1 journal articles
Type Citation Project Document Sources
Journal Article Cohen MD, Sisco M, Baker K, Li Y, Lawrence D, van Loveren H, Zelikoff JT, Schlesinger RB. Effects of inhaled ozone on pulmonary immune cells critical to antibacterial responses in situ. Inhalation Toxicology 2002;14(6):599-619. not available

Supplemental Keywords:

ambient air, ozone, immunotoxicology, pulmonary disease., RFA, Health, Scientific Discipline, Air, Toxicology, Risk Assessments, tropospheric ozone, Biology, cytokine metabolism, pulmonary immunotoxicity, interferons, ozone, pulmonary disease, ambient air, air pollution, pulmonary macrophages, lung inflamation, cell mediated immune response, human exposure, immunotoxicology

Progress and Final Reports:

  • 1998
  • 1999
  • 2000
  • Final