Induction of the proinflammatory cytokine interleukin-18 by axonal injury

✍ Scribed by Til Menge; Sebastian Jander; Guido Stoll

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 727 KB
• Volume: 65
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.1158

✦ Synopsis

Abstract

Interleukin‐18 (IL‐18) is an important cytokine in innate immunity and in the induction phase of autoimmunity. We report the expression of IL‐18 mRNA and protein after nerve crush during Wallerian degeneration (WD) of the rat nervous system. In normal optic nerves (ON) constitutive IL‐18 mRNA levels as revealed by semiquantitative reverse transcriptase polymerase chain reaction were higher than in sciatic nerves (SN). After nerve crush, steady‐state levels moderately increased in the distal nerve part of the SN but not the ON. By immunocytochemistry no SN or faint ON IL‐18 protein expression was detectable in normal nerves. In contrast, IL‐18 expression dramatically increased after SN and ON crush. On the cellular level, ED1^+^ macrophages infiltrating the crush site strongly expressed IL‐18 at days 2 and 4 after SN crush. By days 4 and 8, in addition, the entire distal nerve part was covered by IL‐18^+^ macrophages. At day 16, IL‐18 immunoreactivity had disappeared despite the presistence of large numbers of ED1^+^ macrophages. A similar infiltration of IL‐18^+^ macrophages was seen at the crush site in the ON. Moreover, microglia in the distal ON stump lacking macrophage infiltration and undergoing delayed myelin degradation up‐regulated IL‐18. In conclusion this study shows that IL‐18 is involved in the cytokine network associated with the robust inflammatory response during WD of the SN. Despite up‐regulation of the proinflammatory cytokine IL‐18, major histocompatiblity complex class II, and CD4 molecules similar to macrophages in the PNS, microglial activation after ON injury appears to be insufficient to mount an effective phagocytic response as a prerequisite for successful regeneration in the CNS. J. Neurosci. Res. 65:332–339, 2001. © 2001 Wiley‐Liss, Inc.