Chemokines and peripheral nerve demyelination

It has been speculated that beta-chemokines play a pivotal role in the deve lopment of peripheral nervous system (PNS) disorders characterized by monon uclear cell infiltration. In experimental allergic neuritis (EAN), an anima l model for human Guillain-Barre syndrome (GBS) with mononuclear cell infil tration, we found by quantitative PCR that beta-chemokine messages were upr egulated during the active stage. Moreover, an increase in the monocyte che moattractant protein-1 (MCP-1) message was found in the preclinical stage o f EAN, suggesting the critical role of MCP-l for inducing mononuclear cell infiltrations in this model. Since many cell lineages other than immune cel ls can produce chemokines, this early upregulation of MCP-l may be mediated by non-immune cells, probably endothelia or Schwann cells. To date, apart from MCP-1, only RANTES (Regulated on activation, normal T cell expressed a nd secreted) and macrophage inflammatory protein (MIP)-1 alpha have been ex amined in EAN and found to have similar kinetics of induction. Therefore, u nderstanding the regulation of production of these chemokines as well as me chanisms of inhibiting chemokine/receptor interactions in the PNS may ultim ately lead to disease-specific therapy for GBS and related demyelinating di sorders.