Allergy and asthma: classic TH2 diseases (?)

More than a decade of cytokine immunology has revealed a central role for pro-allergic TH2-like cytokines in the immune pathogenesis of allergic diseases and asthma. Of these, IL-4, IL-5, and IL-13 are produced mostly by T lymphocytes; more recently, numerous other immune cell types have been found capable of producing these cytokines as well, although their role in mediating atopic disease pathogenesis is less well understood. In contrast, the counterregulatory cytokine IFN-gamma can inhibit both the production and activities of the pro-allergic cytokines; therefore, central to the atopic diseases is a paradigm of cytokine imbalance, with overproduction of the TH2-like cytokines, and a relative deficiency of IFN-gamma production. Intriguing recent evidence is that all humans are TH2-like cytokine "skewed" at birth, due to maternal-fetal immune biology imperatives. However, further investigations suggest that IFN-gamma is likely to be pro-inflammatory in many if not most aspects of chronic allergic inflammation. Therefore, our understanding of these "classic TH2" diseases evolves, with important insights that will serve to optimize therapeutic strategies and investigations in the new millennium.