Insulin-like growth factor-1 fails to enhance central nervous system myelin repair during autoimmune demyelination

Previous studies have shown that insulin-like grow-th factor-1 (IGF-1) has beneficial effects, both clinically and histopathologically, on experimenta l autoimmune encephalomyelitis (EAE), although results vary depending on sp ecies and treatment regimen. The present study investigated whether IGF-1, delivered at different time points during the acute and chronic phases of a doptively transferred EAE in SJL mice, had the ability to affect or enhance myelin regeneration. Central nervous system tissue sampled at different st ages of treatment was subjected to detailed neuropathological, immunocytoch emical and molecular analysis. The results revealed some transient clinical amelioration and low level remyelination after IGF-1 administration during the acute phase of EAE, However, central nervous system tissue from acute phase treated animals sampled at chronic time points and from animals given IGF-1 during the chronic phase revealed no enhancing effect on remyelinati on in comparison to vehicle-treated controls. Examination of oligodendrocyt e progenitor populations also revealed no differences between IGF-1- and ve hicle-treated groups. At the cytokine level, the immunomodulatory molecules TGF-beta 2 and TGF-beta 3 displayed significant decreases that may have co ntributed to the transient nature of the effect of IGF-1 on EAE, Together w ith evidence from previous studies, it appears doubtful that IGF-1 is a goo d candidate for treatment in multiple sclerosis, for which EAE serves as a major model.