Autonomic Regulation of Experimental Autoimmune Encephalomyelitis: The Role of Interferon-γ

Objective: The effect of chemical sympathectomy on experimental autoimmune encephalomyelitis (EAE) was studied in interferon-γ (IFN-γ) knockout C57BL/6 mice. Methods: Mice were immunized with myelin oligodendrocyte glycoprotein (MOG)35–55 peptide. Sympathectomy was achieved by subcutaneous administration of 6-hydroxydopamine. Results: We showed previously that wild-type mice developed a mild form of EAE with complete recovery. Sympathectomy caused more serious disease and mice did not recover completely, indicating that the sympathetic nervous system (SNS) downmodulates the process of EAE. The clinical signs of disease were more serious in untreated IFN-γ–/– mice than in wild-type animals. Unexpectedly, sympathectomy resulted in suppression of active EAE in IFN-γ–/– mice, implying that control of actively induced EAE by the SNS depends on INF-γ and the integrity of the cytokine network. We also induced EAE by passive transfer of MOG35–55-reactive lymph node cells, and this disease was aggravated by sympathectomy in both wild-type and knockout animals. Conclusions: Our study supports the idea that the integrity of the whole cytokine network is necessary to maintain normal nervous-immune system interactions.