EXPERIMENTAL ALLERGIC NEURITIS - CYTOLYSIN MESSENGER-RNA EXPRESSION IS UP-REGULATED IN LYMPH-NODE CELLS DURING CONVALESCENCE

Experimental allergic neuritis (EAN) is a T cell mediated animal model of Guillain-Barre syndrome, characterized by inflammation and demyeli nation of the peripheral nervous system (PNS). To study the involvemen t of immunoregulatory cytokines, we induced EAN in Lewis rats by immun izing with bovine PNS myelin (BPM) and Freund's complete adjuvant. mRN A expression of the cytokines IL-1 beta, IL-6, IL-10, IL-12, TNF-alpha and TNF-beta, and the cytolytic effector molecule cytolysin was exami ned in lymph node mononuclear cells (MNC) over the course of EAN by in situ hybridization after culture without antigen and in the presence of BPM, the myelin P2 protein, the control antigen acetylcholine recep tor, or the mitogen PHA. Three patterns of cytokine mRNA expressing MN C in relation to clinical EAN could be distinguished: (i) IL-1 beta mR NA expressing cells peaked already on day 3 post immunization (p.i.), and BPM-and P2-reactive TNF-alpha, and BPM-reactive IL-6 mRNA expressi ng cells were also detected already on day 7 p.i., i.e., before onset of clinical EAN; (ii) BPM-and P2-reactive TNF-alpha peaked together wi th P2-reactive TNF-beta, IL-6 and IL-12 mRNA expressing cells at heigh t of clinical EAN, consistent with a disease-promoting role for these four cytokines; (iii) high levels of BPM- and P2-reactive IL-10 and cy tolysin mRNA expressing cells were observed only during recovery (day 28 p.i.), consistent with a disease down-regulating role of IL-10 and cytolysin. The results suggest a major proinflammatory role for IL-10, TNF-alpha, TNF-beta, IL-6 and IL-12 and a disease down-regulating fun ction of IL-10 as well as cytolysin in EAN. (C) 1997 Elsevier Science B.V.