Cytokine gene polymorphisms in multifactorial diseases: gateways to novel targets for immunotherapy?

Recent advances in cytokine biology have led to novel approaches to the treatment of inflammatory diseases. In this article, we review recent data regarding the role of functional polymorphisms in the genes encoding the prototypic Th1 cytokine interferon gamma and Th2 cytokine interleukin 4 in multifactorial disorders. We have compared genetic data across a heterogeneous assortment of such conditions using a 'haplotype tagging' approach, and demonstrate that cytokine gene association studies are instrumental in the identification of specific disease states or clinical manifestations that are probably caused by genetically determined aberrant cytokine expression. Some of these new findings suggest cytokine effects that go beyond a classical Th1-Th2 dichotomy. Thus, we propose that this information could provide novel targets for immunotherapy and, in particular, might facilitate the identification of clinical subgroups of patients who, by virtue of their genetic constitution at these cytokine gene loci, are more likely to benefit from cytokine agonist or antagonist therapy.