Residual oil fly ash (ROFA), a by-product of fossil fuel combustion and a component of air pollution, has been associated with increased morbidity in susceptible populations. We have shown that soluble metals in ROFA cause lung inflammation and increase susceptibility to infection in rats. The objective was to examine the mechanisms by which soluble metals in ROFA may enhance susceptibility to infection. ROFA was suspended in saline, separated into soluble and insoluble fractions, and the soluble portion (ROFA-SOL) was retained. At day 0, rats were intratracheally instilled (IT) with ROFA (2.0mg/rat) or equivalent quantities of ROFA-SOL, or saline. At day 3, rats were separated into two groups and received an IT dose of either 5x10 4 or 5x10 5 Listeria monocytogenes. Rats were euthanized on days 3 prior to infection, and on days 6, 8, and 10, bronchoalveolar lavage (BAL) was performed on the right lungs, and bacterial clearance was assessed using the left lung. BAL fluid was centrifuged and the supernatant was retained for measurement of cytokine levels. Exposure to ROFA-SOL significantly decreased pulmonary clearance of bacteria at both doses and decreased animal survival after treatment with the high bacterial dose. Prior to bacteria inoculation on day 3, IL-2 was decreased and IL-6 was increased in rats treated with ROFA-SOL compared to saline. After exposure to both doses of bacteria, IL-2 was decreased whereas IL-6 and IL-10 were elevated in ROFA-SOL-treated rats compared to saline. An elevation in IL-6, a pro-inflammatory cytokine associated with the acute phase response, may partially account for the ROFA-SOL-induced inflammation. An increase in IL-10, a cytokine involved in macrophage inhibition, and a reduction in IL-2, a cytokine promoting T-cell growth and proliferation, may result in a suppression of the innate and adaptive immune response to infection, respectively. ROFA and its associated soluble metals alter cytokine production which may affect the ability of the animals to respond to the infection.
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland