ABSTRACT
Allergic inflammation and asthma are both characterized by increased expression of Th2 cytokines such as interleukin (IL)-4, IL-5, IL-9, and IL-13. Immunostimulatory sequences of DNA (ISS DNA) containing CpG motifs (CpG DNA) bind to TLR9 receptors on cells involved in the innate immune response such as plasmacytoid dendritic cells (pDCs), and as a consequence inhibit adaptive Th2 immune responses. ISS DNA therefore represents a potential novel therapeutic strategy to inhibit allergic inflammation and asthma. Studies in mouse and primate models of allergen-induced asthma have demonstrated that ISS DNA inhibits eosinophilic airway inflammation, Th2 cytokine expression, airway hyperreactivity, and features of airway remodeling. Human study data on the use of ISS DNA in allergy and asthma is limited. In a pilot study of subjects with asymptomatic mild asthma, nebulized ISS DNA did not inhibit immediate or late phase airway responses to inhaled allergen challenge. In contrast, in a small Phase II study in human subjects with symptomatic allergic rhinitis, subcutaneous injection of ISS DNA conjugated to a ragweed protein allergen significantly inhibited allergic rhinitis symptoms during the ragweed season. Further studies of ISS DNA in human subjects with allergy and asthma will assist in determining its safety and effectiveness as a therapeutic strategy for such patients.
