Induction of the proinflammatory cytokine interleukin-18 by axonal injury.
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 persistence 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 histocompatibility 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.
Menge
T
T
Department of Neurology, Heinrich-Heine-Universität, Düsseldorf, Germany.
Jander
S
S
Stoll
G
G
D000818:Animals; D001369:Axons / Q000276:immunology* / Q000473:pathology; D020170:Caspase 1 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D017628:Microglia / Q000276:immunology; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000276:immunology*; D020221:Optic Nerve Injuries / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000276:immunology / Q000293:injuries / Q000473:pathology; D014855:Wallerian Degeneration / Q000276:immunology / Q000473:pathology
D020382:Interleukin-18; D012333:RNA, Messenger; D020170:Caspase 1