Immune deviation strategies in the therapy of psoriasis

The experience with biologicals in currently available animal models suggest that inflammatory autoimmune disease depend on IFN-gamma-producing T helper (Th) cells. Deletion of T cells improves most of these autoimmune diseases but bears the risks of general immunosuppression. Alternatively, selective deviation of the inflammatory, disease-inducing Th cells into an anti-inflammatory Th cell phenotype may be a promising strategy to treat inflammatory autoimmune diseases, such as psoriasis, rheumatoid arthritis, multiple sclerosis or autoimmune diabetes. The common feature of these organ-specific autoimmune diseases is the close association with IFN-gamma-producing Th1 cells, which recognize organ-specific antigens and orchestrate the cells and mediators that ultimately cause the tissue damage. Even though the autoantigens recognized in psoriasis remain enigmatic, it has been the first Th1-mediated autoimmune disease successfully treated in humans by immune deviation. The basis of such an immune intervention therapy has been established in experimental mice with model diseases of multiple sclerosis, rheumatoid arthritis or autoimmune diabetes. In all these autoimmune diseases clinical improvement was associated with the skewing of IFN-gamma producing autoantigen-specific Th1 cells into an IL-4 dominated Th2 phenotype. Such Th2 cells are still reactive to the autoantigen but provide a different cytokine pattern. The most powerful cytokines capable of inducing anti-inflammatory Th2 cells are IL-4 itself or IL-11. Interestingly, another agent that has been used for decades in the therapy of psoriasis in some European countries, fumaric acid esters (FAE), seems also to induce immune deviation. This review focuses on the potential immune deviating strategies based on the use of IL-4, IL-11 or FAE in the therapy of psoriasis, the effects of these agents on the immune system, potential risks and future perspectives for therapeutic intervention by immune deviation replacing immunosuppression.