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

Insulin-like growth factors (IGFs) play an important role in development an d myelination in the central nervous system (CNS) as well as in the prolife ration and differentiation of cells of the immune system. To assess the inf luence of this growth factor family on demyelination and repair in multiple sclerosis (MS), the expression of IGF-I, IGF-II, insulin, IGF binding prot eins (IGEBP) 1-3 and IGF-I receptor (IGF-IR) in CNS tissue from MS and norm al control cases was studied by immunocytochemistry. In active MS lesions, the expression of IGF-I, insulin and IGFBP1 was detected in hypertrophic as trocytes while that of IGF-II and IGFBP2 and 3 was confined to foamy macrop hages within lesions and activated microglia in adjacent white matter. IGF- IR, the major IGF receptor, was immunolocalized in macrophages and an astro cyte subpopulation in plaques. Oligodendrocytes in normal-appearing white m atter expressed only IGFBP1, not IGFs or IGF-IR. As the remyelinating capac ity of oligodendrocytes could be impaired owing to the absence of IGF-IR, t he prevailing role of IGFs in inflammatory demyelination may be to promote phagocytosis of myelin and astrogliosis.