Abstract
The application of molecular biology to the discovery of novel pathways to inhibit allergic tissue responses is becoming a reality. Particularly promising approaches are the use of vaccines and pharmacologic agents to downregulate the polarized T Helper (Th)-2 lymphocyte response through enhancement of interferon-γ production. Selective inhibition of specific mediators, such as interleukin (IL)-4, IL-5, IL-13 and eotaxin, should lead to a new class of anticytokine therapeutic agents. At the cellular level, more effective inhibition of mast cell activation and strategies to remove IgE as the triggering stimulus hold promise. With the discovery of susceptibility genes for allergic disease, the next decade is likely to witness substantial further developments in this field, with a strong focus targeted on induction mechanisms and disease prevention. If the current epidemic of allergic disease continues, then there is a strong incentive to identify those environmental factors that are responsible so that appropriate interventions can be introduced. These may include alterations to the maternal and infant diet to program the developing immune response or, in genetically susceptible individuals, the early introduction of a protective vaccine to reset the T lymphocyte balance more in favour of a Th-1 response. In this regard, the development of cytosine and guanosine nucleotide repeats and antigen-specific DNA vaccines look especially promising. In established allergic disease, the task of reversing sensitization is daunting. Safer and more efficacious allergen vaccines, whether using DNA or peptide approaches, offer the most promising approach for fundamentally changing the allergic immune response. Patients would also greatly benefit from more effective and orally active mast cell inhibitors and small molecules that could either remove IgE or effectively interrupt its capacity to signal through its cell surface receptors. In the meantime, the epidemic of allergic disease requires urgent attention, not only in the provision of specialist centers for providing accurate diagnosis and for administering treatment (including immunotherapy), but in a clear recognition that these disorders are caused by changing environmental factors and, as a consequence, deserve attention at the level of public health.
