Insulin-like growth factor-1 fails to enhance central nervous system myelin repair during autoimmune demyelination.
Previous studies have shown that insulin-like growth factor-1 (IGF-1) has beneficial effects, both clinically and histopathologically, on experimental autoimmune encephalomyelitis (EAE), although results vary depending on species and treatment regimen. The present study investigated whether IGF-1, delivered at different time points during the acute and chronic phases of adoptively transferred EAE in SJL mice, had the ability to affect or enhance myelin regeneration. Central nervous system tissue sampled at different stages of treatment was subjected to detailed neuropathological, immunocytochemical 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 remyelination in comparison to vehicle-treated controls. Examination of oligodendrocyte progenitor populations also revealed no differences between IGF-1- and vehicle-treated groups. At the cytokine level, the immunomodulatory molecules TGF-beta2 and TGF-beta3 displayed significant decreases that may have contributed to the transient nature of the effect of IGF-1 on EAE. Together with evidence from previous studies, it appears doubtful that IGF-1 is a good candidate for treatment in multiple sclerosis, for which EAE serves as a major model.
Cannella
B
B
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, New York 10461-1602, USA. cannella@aecom.yu.edu
Pitt
D
D
Capello
E
E
Raine
C S
CS
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use
D016207:Cytokines; D011994:Recombinant Proteins; D012313:RNA; D007334:Insulin-Like Growth Factor I