Enhanced Allergic Sensitization in Animals Exposed to Particulate Air Pollution

Abstract

Epidemiological studies have found an association between elevated levels of particulate matter (PM) air pollution and increased medication use and hospital visits by asthmatics. While it is known that asthmatics are generally more sensitive to airborne contaminants such as sulfur dioxide and tobacco smoke, it is difficult to test which components of air pollution may also contribute to the induction of pulmonary allergy (sensitization) because of the risk in creating disease. Recent studies in mice and rats, however, have demonstrated that pulmonary exposure to combustion particles such as diesel and residual oil fly ash (ROFA) can exacerbate immunological sensitization (in the form of immunoglobulin E antibody and lymphocyte reactivity) to experimental and natural allergens. Subsequent allergen challenge in these animals results in a greater allergen-induced bronchoconstriction, elevated numbers of eosinophils in the lung, and enhanced airway responsiveness to cholinergic agents compared to what occurs in similarly immunized animals pretreated with vehicle or "inert" particles. Although the mechanisms for these effects are not known, it has been demonstrated that the adjuvant effects of diesel and ROFA can be reproduced with hydrocarbons and soluble transition metals from diesel and ROFA, respectively. In addition, analysis of mediator expression and release over the sensitization phase has revealed that PM exposure can enhance production of Th2 cytokines such as interleukin-5 (IL-5) and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). These experimental systems demonstrate the potential of particulate air pollutants to enhance allergic sensitization and can be further used to elucidate the mechanism for these effects.