Premium
The cytokine network of Wallerian degeneration: IL‐10 and GM‐CSF
Author(s) -
Be′eri Hadassah,
Reichert Fanny,
Saada Ann,
Rotshenker Shlomo
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00277.x
Subject(s) - wallerian degeneration , myelin , granulocyte macrophage colony stimulating factor , phagocytosis , immunology , macrophage , microbiology and biotechnology , schwann cell , cytokine , biology , chemistry , neuroscience , central nervous system , biochemistry , in vitro
Wallerian degeneration (WD) is the inflammatory response of peripheral nerves to injury. Evidence is provided that granulocyte macrophage colony stimulating factor (GM‐CSF) contributes to the initiation and progression of WD by activating macrophages and Schwann, whereas IL‐10 down‐regulates WD by inhibiting GM‐CSF production. A significant role of activated macrophages and Schwann for future regeneration is myelin removal by phagocytosis and degradation. We studied the timing and magnitude of GM‐CSF and IL‐10 production, macrophage and Schwann activation, and myelin degradation in C57BL/6NHSD and C57BL/6‐WLD/OLA/NHSD mice that display normal rapid‐WD and abnormal slow‐WD, respectively. We observed the following events in rapid‐WD. The onset of GM‐CSF production is within 5 h after injury. Production is steadily augmented during the first 3 days, but is attenuated thereafter. The onset of production of the macrophage and Schwann activation marker Galectin‐3/MAC‐2 succeeds that of GM‐CSF. Galectin‐3/MAC‐2 production is up‐regulated during the first 6 days, but is down‐regulated thereafter. The onset of myelin degradation succeeds that of Galectin‐3/MAC‐2, and is almost complete within 1 week. IL‐10 production displays two phases. An immediate low followed by a high that begins on the fourth day, reaching highest levels on the seventh. The timing and magnitude of GM‐CSF production thus enable the rapid activation of macrophages and Schwann that consequently phagocytose and degrade myelin. The timing and magnitude of IL‐10 production suggest a role in down‐regulating WD after myelin is removed. In contrast, slow‐WD nerves produce low inefficient levels of GM‐CSF and IL‐10 throughout. Therefore, deficient IL‐10 levels cannot account for inefficient GM‐CSF production, whereas deficient GM‐CSF levels may account, in part, for slow‐WD.