MS is a neurodegenerative autoimmune disease of the white matter of the CNS in which cytokines have an important role. Some cytokines, such as IL-6, IL-17, TGF-β, and IFN-γ, trigger an inflammatory response in the white matter of the brain. Such inflammatory responses contribute to the development of plaques (the characteristic pathology of MS) in the white matter by stripping myelin from neurons. Other molecules that regulate cytokines (e.g., osteopontin [OPN]) may increase Th17 and IFN-γ production. In addition, the most popular treatment for individuals with MS is the cytokine IFN-β, which is though to attenuate the action of the proinflammatory cytokines. Depicted are other potential therapies that may involve blockade of IFN-γ, IL-6, IL-12, or IL-23. Therapies aimed at blocking the adaptive immune response include DNA vaccination to induce tolerance. Statins and Copaxone are aimed at treatment of innate immune pathways and at the immune synapse. The most potent approved therapy for MS, natalizumab, blocks α₄β₁ integrin (verly late antigen 4 [VLA4]) interactions with VCAM. Depletion of B cells with anti-CD20 may be a promising therapeutic approach (all these approaches are discussed in refs. 29, 63, and 64). Adapted with permission from Nature Reviews. Immunology (23).