Immune modulation for treatment of allergic disease

Immune modulation for treatment of allergic diseases aims to decrease the pathologic immune response rather than to cause a return to an immunologically naive or unresponsive state. Our expanding knowledge of innate and adaptive immune responses at the molecular level has led to development of immunomodulators for several allergic diseases, particularly asthma, allergic rhinitis, and eosinophilic esophagitis. Although successful immune modulation in mouse models of allergic disease have often failed to translate into significant results in human clinical trials, much has been learned about the pleotropic nature of cytokines and their effector mechanisms and of the varied phenotypes of allergic disease. We examine strategies of immune modulation in allergic diseases that have undergone human clinical trials, all with the common goal of decreasing the T-helper 2 (Th2) response, but through different mechanisms: blocking critical Th2 cytokines, inhibiting Th2 cytokine synthesis, blocking critical Th2 effector molecules, inhibiting important cells in the Th2 response, and stimulating Th1 responses. Therapies directed against specific effector molecules, such as immunoglobulin E and prostaglandin D2, hold promise in immune modulation of allergic disease, as do targeting the IL-4/IL-13 receptor and augmenting Th1/Th2 balance with Toll-like receptor agonists.