Protective role of interleukin-10 in ozone-induced pulmonary inflammation.

BACKGROUND: The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. OBJECTIVES: We investigated the molecular mechanisms underlying interleuken-10 (IL-10)-mediated attenuation of O3-induced pulmonary inflammation in mice. METHODS: Il10-deficient (Il10(-/-)) and wild-type (Il10(+/+)) mice were exposed to 0.3 ppm O3 or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation. RESULTS: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10(-/-) mice than in Il10(+/+) mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10(-/-) compared with Il10(+/+) mice. Gene expression analyses revealed several IL-10-dependent and O3-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3. CONCLUSIONS: Results indicate that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.

Induction of asthma and the environment: what we know and need to know.

The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop "Environmental Influences on the Induction and Incidence of Asthma" to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment.