New therapeutic strategies in allergic diseases.

Abstract

During the past 10 years, strong evidence has been provided to suggest that type 2 T herpes (Th2) responses to 'innocuous' environmental antigens (allergens) play a critical triggering role in the development of allergic disorders. The important role of Th2 cytokines, IL-4, IL-5, IL-9, IL-13, in accounting for most pathophysiological manifestations of atopic allergy has been largely clarified by a series of studies performed in both human diseases and experimental animal models of allergy and asthma. Moreover, the mechanisms responsible for Th2-polarized responses against allergens in atopic subjects, as well as the nature of transcription factors involved in the Th2 polarization, have been identified. Likewise, the role of chemoattractants and chemoattractant receptors, as well as of adhesion molecules, in favoring and amplifying the allergic inflammation has been established. The new insights into the pathophysiology of T cell responses in atopic diseases are providing exciting opportunities for the development of novel immunotherapeutic strategies. These include either nonallergen-specific or allergen-specific regimens. In patients with severe atopic disorders, the possibility of nonallergen-specific strategies designed to target Th2 cells; molecules involved in Th2 differentiation, such as Th2-selective transcription factors, or Th2-dependent effector molecules, such as Th2 cytokines, IL-4, IL-5, IL-9, and IL-13; Th2-related chemokines and/or receptors, or IgE antibody, are being considered. In the majority of atopic subjects affected by mild or moderate allergic diseases, allergen-specific immunotherapies probably would be better. To that end, there are presently two main lines of research, one based on the induction of immune suppression and the other on the redirection of allergen-specific Th2 cell responses to a less polarized profile of cytokine production (immune deviation).