Autonomic regulation of experimental autoimmune encephalomyelitis in IL-4 knockout mice.
The effect of chemical sympathectomy induced with 6-hydroxydopamine (OHDA) on experimental autoimmune encephalomyelitis (EAE) was studied in wild type and IL-4-/- C57BL/6 (B6) mice. When actively sensitized with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide, control B6 mice developed a mild form of EAE with full recovery. The sympathectomized mice developed paralysis with higher maximum disease score and did not recover completely, indicating that the sympathetic nervous system (SNS) down-modulates the process of EAE. Unexpectedly, however, sympathectomy resulted in suppression of EAE in IL-4-/- mice, implying that control of actively induced EAE by the SNS depends on the genetic background of mice. We also induced EAE by passive transfer of MOG35-55-reactive lymph node cells, and this disease was augmented by sympathectomy in both wild type and knockout animals. Further experiments showed that changes in T cell populations and the activity of antigen presenting cells might be responsible for the altered immune response and clinical course after sympathetic ablation. Our studies indicate that the absence of a single cytokine can severely alter nervous-immune system interactions.
Pál
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Division of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.
Yamamura
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T
Tabira
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D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016627:Oxidopamine / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D013562:Sympathectomy; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors
D010455:Peptides; D015847:Interleukin-4; D007371:Interferon-gamma; D016627:Oxidopamine