Insulin-like growth factors and binding proteins in multiple sclerosis plaques

Insulin-like growth factors (IGFs) play an important role in development and myelination in the central nervous system (CNS) as well as in the proliferation and differentiation of cells of the immune system. To assess the influence of this growth factor family on demyelination and repair in multiple sclerosis (MS), the expression of IGF-I, IGF-II, insulin, IGF binding proteins (IGFBP) 1-3 and IGF-I receptor (IGF-IR) in CNS tissue from MS and normal control cases was studied by immunocytochemistry. In active MS lesions, the expression of IGF-I, insulin and IGFBP1 was detected in hypertrophic astrocytes while that of IGF-II and IGFBP2 and 3 was confined to foamy macrophages within lesions and activated microglia in adjacent white matter. IGF-IR, the major IGF receptor, was immunolocalized in macrophages and an astrocyte subpopulation in plaques. Oligodendrocytes in normal-appearing white matter expressed only IGFBP1, not IGFs or IGF-IR. As the remyelinating capacity of oligodendrocytes could be impaired owing to the absence of IGF-IR, the prevailing role of IGFs in inflammatory demyelination may be to promote phagocytosis of myelin and astrogliosis.