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.