Immune stimulatory strategies for the prevention and treatment of asthma.

The severity and incidence of asthma has dramatically increased in the developed nations over the last decades. Although the reason for this development is unknown, epidemiological studies and experimental data have lead to the suggestion that this phenomenon is associated with the decline of infectious diseases, which induce T helper 1 and/or T regulatory responses. Supporting this view are recent publications showing that animals can be protected from developing asthma by using different immune stimulatory strategies. One approach is based on vaccinations using live or killed bacteria or their components, CpG-ODNs or DNA vaccination, which all induce allergen-specific or unspecific Th1 responses. Th1 responses lead to the production of IFN-gamma, IL-12, IL-18 and IL-23, thereby inhibiting Th2 responses and thus the development of asthma. A further strategy both for the prevention and therapy of asthma is the induction of Tr cells. Tr cells have also been shown to suppress allergic Th2 responses, however, in contrast to Th1 cells through a cell/cell contact mediated mechanism or by the secretion of the anti-inflammatory cytokines IL-10 and/or TGF-beta. Furthermore, there is growing information on how to induce Tr cells both in animals and humans. Here we review the data showing that animals can be protected from developing asthma by immune stimulation leading to Th1 or Tr responses. Possible future human use and safety of the described strategies are also discussed.