CNS Drug Reviews

Cytokines had originally been thought to be glycoproteins functioning largely in hematolymphopoiesis and immune reaction. In the 1990s, there have been an increasing number of reports showing that cytokines also play important roles in other organs and tissues, including the nervous system. Now the concepts of the nervous system as an immunologically privileged site have been significantly modified (62). Most cytokines are produced and have several functions in the nervous system (24,63). Among these several functions, many neuroscientists have focused on the trophic or protective (48), and inversely toxic (62,73), influences on neurons. Lack of such cytokines or excesses have been thought to be important with respect not only to etiologies and pathogenesis but also to developing therapies for several neurologic disorders (45,62,77). In fact, cytokines have been reported to be involved in the etiopathogenesis of several neurologic disorders (14,32,45,53,59,63,78), suggesting that analyses of cytokine functions in the nervous system are important: 1) to clarify the precise mechanisms deciding the direction in bidirectional effects (trophic and toxic) of cytokines on neurons; and 2) to modify the pathologies of neurologic diseases and delay their progression. However, clinical trials based on such a hypothesis have been restricted to a few neurologic disorders, for example, amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), using a very limited number of cytokines such as ciliary neurotrophic factor (CNTF), insulin-like growth factor I (IGFI), and interferons (IFNs) (19,77). In addition, the pharmacology, pharmacokinetics, and ad-