Autonomic regulation of experimental autoimmune encephalomyelitis: the role of interferon-gamma.
OBJECTIVE
The effect of chemical sympathectomy on experimental autoimmune encephalomyelitis (EAE) was studied in interferon-gamma (IFN-gamma) 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-gamma(-/-) mice than in wild-type animals. Unexpectedly, sympathectomy resulted in suppression of active EAE in IFN-gamma(-/-) mice, implying that control of actively induced EAE by the SNS depends on INF-gamma and the integrity of the cytokine network. We also induced EAE by passive transfer of MOG(35-55)-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.
Pál
Edre
E
Division of Demyelinating Disease and Aging, National Institute of Neuroscience, Kodaira, Tokyo, Japan. pale@neuro.pote.hu
Tabira
Takeshi
T
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D015213:Neuroimmunomodulation / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013563:Sympathectomy, Chemical
D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma