DNA, the Immune System, and Atopic Disease

Abstract

The prevalence and severity of atopic diseases (atopic dermatitis, asthma, and allergic rhinitis) have increased over recent decades, particularly in industrialized nations. Atopic dermatitis, like asthma, is more common in older siblings and in less crowded houses and with late entry to day care, increased maternal education, and higher socio-economic status. The inverse relationship between the incidence of atopy and childhood infections has led to the "hygiene hypothesis," which suggests that diminished exposure to childhood infections in modern society has led to decreased TH1-type responses. Reduced TH1 may lead to enhanced TH2-type inflammation, which is important in promoting asthma and allergic disease. Corticosteroids, commonly used to treat these conditions, inhibit the function of inflammatory cells, but they are ineffective in altering the initial TH2-type response to allergens in a sensitized individual. Treatment with TH1 cytokines not only has failed to make any significant impact on the outcome of these diseases, but it also has caused significant adverse reactions. A novel therapeutic approach, recently reported in the preclinical setting, is the use of oligodeoxynucleotides, which contain unmethylated motifs centered on CG dinucleotides. These CpG oligodeoxynucleotides potently induce TH1 cytokines and suppress TH2 cytokines, and can prevent manifestations of asthma and other allergic diseases in animal models. They have the potential to reverse TH2-type responses to allergens and thus restore balance to the immune system without the adverse effects of TH1 cytokines.