Immunomodulation in asthma: mechanisms and possible pitfalls

Atopic diseases, including atopic asthma, are characterized by T helper cell (Th)2 cytokine pathology. The increased prevalence of asthma and allergic diseases, as well as Th1-associated conditions, is linked to 'excessive' hygiene. Several new immunomodulatory strategies in asthma and allergy, such as peptide therapy and DNA vaccines, show promise and are under clinical evaluation. They appear to exert their effects by producing a Th2 to Th1 shift, as well as inducing regulatory cytokines such as interleukin-10 and transforming growth factor-beta. There is no evidence that such approaches are associated with Th1 pathology in humans, although lung inflammation induced by Th1 cells has been observed in mice. IL-10 plays a key regulatory role in dampening both Th2- and Th1-associated diseases. Failure to stimulate regulatory responses could explain the rising trends in allergy and autoimmunity, and also partly explain the mode of action of allergen-injection immunotherapy and new immunomodulatory approaches.