Systemic inflammation induces axon injury during brain inflammation

Area of Science:

• Neuroimmunology
• Infectious Disease Immunology

Background:

• Axon injury significantly contributes to disability progression in multiple sclerosis (MS).
• Systemic infections are frequently observed before MS relapses and linked to Alzheimer's disease progression.
• The innate immune system, particularly macrophage activation, plays a role in axonal injury within MS lesions.

Purpose of the Study:

• To investigate the hypothesis that systemic inflammation enhances axonal damage in MS through innate immune system activation.
• To explore the impact of systemic inflammation on the central nervous system (CNS) innate immune response in a model of MS.

Main Methods:

• Experimental allergic encephalomyelitis (EAE), a model for MS, was induced in Lewis rats.
• Rats received a systemic challenge with lipopolysaccharide (LPS) or saline during the remission phase.
• Clinical outcomes, cellular infiltration, tissue damage, and cytokine profiles were assessed.

Main Results:

• Systemic inflammation activated the CNS innate immune response, altering macrophage/microglia phenotype.
• This activation led to increased expression of inducible nitric oxide synthase (iNOS) and interleukin-1β (IL-1β).
• Elevated axon injury was observed, independent of overt clinical relapse.

Conclusions:

• Microglia/macrophages in CNS lesions respond to peripheral inflammatory signals by producing immune mediators that cause tissue damage.
• Preventing and managing systemic infections in individuals with MS may be crucial for slowing disease progression.