Introductory remarks: immunosuppressive and immunomodulating drugs,where and how do they act?

Immunotherapies used in multiple sclerosis are reviewed. The mechanisms of action supporting their clinical application are described according to our current understanding. Immune treatments can be divided into three groups: (1) cytostatic and cytotoxic immunosuppressants which block the cell cycle of immunocompetent cells and/or provoke their deletion; (2) immunomodulatory which specifically interfere in cellular or humoral immune mechanisms; (3) immunoregulators which restore immunodeficient states but have also immunosuppressive properties at the same time. Numerous attempts have been made to correct almost all abnormal immune mechanisms underlying disease progression. The results of those clinical trials are reviewed. Recent studies have demonstrated that a severe, unspecific and sustained immunosuppression markedly downregulates the clinical and pathological activity of the disease. Unfortunately, serious delayed adverse effects prevent a long-term administration. Recent specific immunomodulators with an acceptable toxicity have provided modest but unquestionable benefit on the attack rate and MRI lesion burden. No dear effect on progression has been demonstrated to date. There is still much work to be done to improve the efficacy of our current therapies on the attack rate and particularly on the progression. Several promising new compounds are already under evaluation. Another approach is combination therapies which will certainly become critical in MS like in other autoimmune diseases.