Systemic inflammation induces axon injury during brain inflammation

Moreno, Beatriz, Jukes, John-Paul, Vergara-Irigaray, Nuria, Errea, O., Villoslada, Pablo, Perry, V.H. and Newman, T.A. (2011) Systemic inflammation induces axon injury during brain inflammation. Annals of Neurology, 70 (6), 932-942. (doi:10.1002/ana.22550). (PMID:22190366)

Abstract

Objectives: axon injury is a key contributor to the progression of disability in multiple sclerosis (MS). Systemic infections, which frequently precede relapses in MS, have been linked to clinical progression in Alzheimer's disease. There is evidence of a role for the innate immune system in MS lesions as axonal injury is associated with macrophage activation. We hypothesize that systemic inflammation leads to enhanced axonal damage in MS as a consequence of innate immune system activation.

Methods: monophasic experimental allergic encephalomyelitis (EAE) was induced in a cohort of Lewis rats. The animals received a systemic challenge with either an inflammogen (LPS) or saline as a control, at 1, 3 or 6 weeks into the remission phase of the disease. The clinical outcome, cellular recruitment to lesions, degree of tissue damage and cytokine profiles were measured.

Results: we found that systemic inflammation activates the central nervous system (CNS) innate immune response and results in a switch in the macrophage/microglia phenotype. This switch was accompanied by iNOS and IL-1? expression and increased axon injury. This increased injury occurred independently of the re-emergence of overt clinical signs.

Interpretation: our evidence indicates that microglia/macrophages, associated with lesions, respond to circulating cytokines, produced in response to an inflammatory event outside the CNS, by producing immune mediators that lead to tissue damage. This has implications for people with MS, where prevention and stringent management of systemic infectious diseases may slow disease progression

This record has no associated files available for download.

Contributors

Author: T.A. Newman

Download statistics