Autonomic regulation of experimental autoimmune encephalomyelitis in IL-4 knockout mice

Abstract

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 MOG 35–55-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.