Reactive oxygen species and allergic responses

Abstract

There is much persuasive evidence that reactive oxygen species (ROS) are significant harmful mediators in asthma and allergic diseases. Exposure of the airway epithelium to particulate matter such as diesel exhaust particles, ultrafine particles, and pollens induces ROS. Pollens contain an intrinsic NADPH oxidase that induces ROS and mitochondrial dysfunction that contribute to innate induction of allergic inflammation. DNA damage induced by ROS induces the release of 8-oxoguanine (8-oxoG) from damaged DNA. The damaged base is cleaved off by the 8-oxoguanine-DNA glycosylase-1 (OGG1), and 8-oxoG and OGG1 bind to form a signaling complex that activates NF-kB and airway inflammation. Human studies have shown that asthma is associated with high levels of ROS and lipid peroxides. Allergen challenge in subjects with asthma induces ROS locally in the airways. Observational and interventional studies have revealed conflicting data or a non-beneficial role of vitamin C in asthma and allergic diseases. Most observational studies of vitamin E have shown some effect of vitamin E supplementation in improving respiratory outcomes in asthma/atopic subjects, and limited interventional studies support these observational findings. An important limitation of orally administered antioxidants like vitamin C and tocopherol is that very little is delivered to the site of inflammation in the airways to enhance the local antioxidant potential. Pharmaceutical companies need to focus their efforts on developing orally administered or inhaled products that will augment local antioxidant levels in the airways, thereby augmenting their efficacy in the prevention of asthma and allergic diseases.