Residual oil fly ash amplifies allergic cytokines, airway responsiveness, and inflammation in mice

Particulate matter (PM) air pollution may increase symptom severity in alle rgic asthmatics. To examine possible interaction, or greater than additive responses, between PM effects and allergic responses, an ovalbumin-sensitiz ed and challenged (OVA) mouse model of allergic airways disease was utilize d. After challenge, mice were intratracheally instilled with saline vehicle or 3 mg/kg (similar to 60 mu g) residual oil fly ash (ROFA), a transition metal-rich emission source PM sample. Physiological and inflammatory respon ses were examined 1, 3, 8, and 15 d later. In response to intravenously adm inistered methacholine, ROFA increased total respiratory system resistance and decreased compliance 1 d after exposure, whereas effects of OVA lasted at least 15 d after exposure. Significant interactions between OVA and ROFA were mainly observed 8 d after challenge and exposure, especially with res pect to compliance. A strong interaction (p < 0.01) between OVA and ROFA ex posure resulted in 8-fold (1 d) and 3-fold (3 d) increases in bronchoalveol ar lavage (BAL) fluid eosinophil numbers. A similarly strong interaction (8 -fold) was observed in BAL fluid interleukin-4 (IL-4) 1 d after challenge a nd exposure. Significant though less strong interactions were also found wi th respect to IL-4 and IL-5 by 3 d postchallenge/exposure. This study shows that allergen challenge and exposure to emission source particulate matter containing relatively high levels of transitions metals can interact to in crease Th2 cytokine production, eosinophil recruitment, and airway hyperres ponsiveness in previously sensitized mice.