Inhalation of Fine and Ultrafine, but not Coarse, Particles from Mexico City Induces Inflammatory Lung Response in Rats

Debray-García Y. (1), Acosta-Saavedra L. (1), Uribe-Ramirez M. (1), Guerra-Garcia R. (1), Uriarte-Ramos A. G. (1), Hernández Zavala A. (1), Razo-Garcia A. (1), Calderón-Aranda E. (1), Eigueren-Fernandez A. (2), Salazar K. (3), Gookin G. (3), Kleinman M. (3), De Vizcaya-Ruiz A. (1).

(1) Departament of Toxicology, CINVESTAV-IPN, Mexico City, MX; (2)Center for Occupational and Environmental Health, School of Public Health, University of California-Los Angeles, Los Angeles, CA, USA; (3) Division of Occupational and Environmental Medicine, Department of Medicine, University of California-Irvine, Irvine, CA, USA.

     Abstract Number: 156
     Last modified: November 6, 2009

Abstract
Exposure to particulate matter (PM) contributes to the development of airway and pulmonary diseases, including chronic obstructive pulmonary disease (COPD), chronic bronchitis and asthma, among others, all of them related to acute and chronic inflammatory response in which the level of proinflammatory cytokines rises. Mexico City is a city with notable air pollution problems. A number of days in the year (35 days for PM10 and 138 for PM2.5 in 2007) the national air quality standards are exceeded, resulting in a significant health risk for the population. The objective of this study was to evaluate PM-induced lung inflammation in rats exposed to PM in Mexico City. Four groups of 6 male Sprague-Dawley rats were exposed to filtered air (FA), coarse (C), fine (F), and ultrafine (UF) PM for 3 days (5h/day) and 8 weeks (5h/day for 4 days/week) using a versatile aerosol concentration enrichment system (VACES) in the spring of 2009. Cytokines associated with lung inflammatory responses (IL-1beta, IL-6, MIP-2 and TNF-alpha) were determined in bronchoalveolar lavage fluid (BALF) using ELISA. Exposure for 3 days to C particles did not induce any of the proinflammatory cytokines; however, an increased expression of IL-1beta, IL-6 and MIP-2 from the exposure to F and UF particles was observed, probably due to acute lung damage. TNF-alpha concentrations were elevated after 3 day of exposure to UF PM, but the effect was not statistically significant. TNF-alpha has a short lifetime and is one of the first mediators elicited by the immune response and we might have missed the peak concentration. TNF-alpha is an important mediator for the synthesis of other cytokines that also participate in acute inflammatory response, such as IL-6. Exposure for 8 weeks to C, F and UF showed a significant reduction in IL-1beta and IL-6 compared to FA, but MIP-2 continued to be elevated after exposure to UF. No significant changes in TNF-alpha concentration were observed. The decrease in proinflamatory cytokines after 8 weeks of exposure suggests a suppressed immune response that increases lung infection susceptibility. In conclusion, acute exposure to F and UF particles induces an acute lung inflammatory response that evolves to suppression of immune responses increasing infection susceptibility after sub-chronic (8-week) exposures. Considering the large population exposed to elevated levels of PM in Mexico City, the exposure to F and UF particles should be explored as a risk factor associated to the high incidence of respiratory morbidity and mortality in Mexico City, as well as increased susceptibility to infectious agents, potentially contributing to crises such as that caused by the influenza virus in May 2009.