Cytokine dichotomy in peripheral nervous system influences the outcome of experimental allergic neuritis: dynamics of mRNA expression for IL-1 beta, IL-6, IL-10, IL-12, TNF-alpha, TNF-beta, and cytolysin

Autor(es): Zhu J,Bai X F,Mix E,Link H

Resumo: Experimental autoimmune neuritis (EAN) is a T-cell-mediated autoimmune disease of the peripheral nervous system (PNS) that can be actively induced in Lewis rats by immunization with bovine PNS myelin and Freund's complete adjuvant. EAN is used as an animal model of the Guillain-Barré syndrome (GBS) in humans. To study the potential role of cytokines in EAN, we used in situ hybridization to detect mRNA expression of interleukin 1 beta (IL-1 beta), IL-6, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, and cytolysin in sciatic nerve sections over the course of EAN. Cells expressing IL-1 beta and IL-6 mRNA appeared early and peaked on Day 7 postimmunization (p.i.), i.e., at onset of clinical signs of EAN, consistent with a role of these cytokine in an early immune response leading to autoaggressive immunity in EAN. TNF-alpha, TNF-beta, and IL-12 mRNA expression was maximally upmodulated on Day 14 p.i., i.e., at height of clinical EAN, favoring a role for these cytokines in disease development. On the contrary, transcription of cytolysin and IL-10 in sciatic nerves reached maxima during clinical improvement of EAN. The data argue for a major proinflammatory role for IL-1 beta, IL-6, TNF-alpha, TNF-beta, and IL-12 and a disease downregulating function for both cytolysin and IL-10 at the target site in EAN. These findings have relevance for future studies on pathogenesis and treatment of GBS in humans.

Imprenta: Clinical Immunology and Immunopathology, v. 84, n. 1, p. 85-94, 1997

Identificador do objeto digital: 10.1006/clin.1997.4356

Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Biochemistry ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - RNA ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Immunology

Data de publicação: 1997