Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration

Axon loss in the CNS is characteristic of many neurodegenerative diseases but the mechanisms of axon degeneration are poorly understood. In particular, we know little of the inflammatory response triggered by CNS axon degeneration with comparison to that provoked by death of the neuronal cell body. We show that Wallerian degeneration of the mouse optic nerve induces transcription of TGF-beta 1 and TNF-alpha, but not proinflammatory cytokines IL-1 beta and IL-6 and microglial activation. This atypical inflammatory response resembles macrophages that have phagocytosed apoptotic cells and prion-infected CNS. Significantly, peripheral endotoxin challenge after injury switched this profile by inducing IL-1 beta, IL-6 transcripts, other inflammation-associated products and reducing neurofilament immunoreactivity. We propose that microglia are activated by Wallerian degeneration and persist in an atypical but primed state and can be switched by systemic inflammation to provoke a classical proinflammatory profile with potentially deleterious consequences. Crown Copyright (C) 2007 Published by Elsevier Inc. All rights reserved.