Intravenous immunoglobulin ameliorates experimental autoimmune encephalomyelitis and reduces neuropatholopical abnormalities when administered prophylactically

Background and methods: Immunomodulation with intravenous immunoglobulin (IVIG) represents a way of interfering with the disease process in multiple sclerosis (MS). In this study, the effects of IVIG on neurological symptoms and central nervous system (CNS) pathology were evaluated in experimental autoimmune encephalomyelitis (EAE), an MS animal model. EAE was induced in susceptible Dark Agouti rats by active immunization with a spinal cord homogenate, and infusions of 1 g/kg IVIG were given prophylactically or therapeutically. Results: The administration of IVIG at the time of immunization significantly suppressed the development of neurological symptoms compared with infusions of placebo (mean EAE score 0.6 +/- 0.3 versus 2.3 +/- 0.4). Moreover, the prophylactic IVIG administration resulted in a significant inhibition of the inflammatory response in CNS tissue (inflammation score 1.1 +/- 0.2 versus 1.8 +/- 0.2 after placebo). No beneficial effects were obtained by therapeutic IVIG infusions as the EAE disease course and the degree of inflammation and demyelination in the CNS were not different from animals receiving treatment with placebo. Conclusions: The present study indicates that IVIG reduces the symptoms of EAE by suppression of the CNS inflammation that characterizes CNS pathology in these animals. Taking into account data from clinical trials of IVIG in MS, the results further suggest that IVIG acts primarily during the induction phase of the immune response thus preventing the development of relapses in MS.