CYTOKINE DICHOTOMY IN PERIPHERAL NERVOUS-SYSTEM INFLUENCES THE OUTCOME OF EXPERIMENTAL ALLERGIC NEURITIS - DYNAMICS OF MESSENGER-RNA EXPRESSION FOR IL-1-BETA, IL-6, IL-10, IL-12, TNF-ALPHA, TNF-BETA, AND CYTOLYSIN

Experimental autoimmune neuritis (EAN) is a T-cell-mediated autoimmune disease of the peripheral nervous system (PNS) that can be actively i nduced in Lewis rats by immunization with bovine PNS myelin and Freund 's complete adjuvant. EAN is used as an animal model of the Guillain-B arre syndrome (GBS) in humans. To study the potential role of cytokine s in EAN, we used in situ hybridization to detect mRNA expression of i nterleukin 1 beta (IL-1 beta), IL-6, IL-10, IL-12, tumor necrosis fact or-alpha (TNF-alpha), TNF-beta, and cytolysin in sciatic nerve section s over the course of EAN. Cells expressing IL-1 beta and IL-6 mRNA app eared early and peaked on Day 7 postimmunization (p.i.), i.e., at onse t of clinical signs of EAN, consistent with a role of these cytokine i n an early immune response leading to autoaggresive immunity in EAN. T NF-alpha, TNF-beta, and IL-12 mRNA expression was maximally upmodulate d on Day 14 p.i., i.e., at height of clinical EAN, favoring a role for these cytokines in disease development. On the contrary, transcriptio n of cytolysin and IL-10 in sciatic nerves reached maxima during clini cal improvement of EAN. The data argue for a major proinflammatory rol e for IL-1 beta, IL-6, TNF-alpha, TNF-beta, and IL-12 and a disease do wnregulating function for both cytolysin and IL-10 at the target site in EAN. These findings have relevance for future studies on pathogenes is and treatment of GBS in humans. (C) 1997 Academic Press.