REGULATION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS WITH INSULIN-LIKE-GROWTH-FACTOR (IGF-1) AND IGF-1 IGF-BINDING PROTEIN-3 COMPLEX (IGF-1 IGFBP3)/

Insulin-like growth factor (IGF)-1 is a cytokine that promotes oligode ndrocyte development and myelin production. This study investigated wh ether treatment of chronic, relapsing murine experimental autoimmune e ncephalomyelitis (EAE) with IGF-1 or IGF-1 associated with its binding protein, IGFBP3, altered the course of disease. Administration of IGF -1/IGFBP3 (1-100 mg/kg per day) delayed the onset of disease in a dose -dependent manner and histologic examination showed a delay in inflamm atory cells entering the central nervous system. However, once signs o f EAE developed, disease was enhanced in the mice that had been given the highest dose of IGF-1/IGFBP3. Treatment with IGF-1/IGFBP3 after th e onset of signs resulted in a severe relapse. Administration of free IGF-1 (10 mg/kg per day) provided mild protection when given before di sease onset, but did not significantly alter the course of disease if given after disease onset. Possible mechanisms that could explain the altered disease in IGF-1/IGFBP3-treated mice included (a) IGF-1/IGFBP3 administration delayed the onset of EAE by downregulating ICAM-1 gene expression in the central nervous system, and (b) IGF-1/IGFBP3 treatm ent of EAE resulted in more severe disease due to enhanced expansion o f encephalitogenic T cells. Although IGF-1 may enhance remyelination, these results indicate that administration of IGF-1 associated with IG FBP3 may also accentuate autoimmune demyelinating disease.