Epub: Murta et al. CNS response to a second pro-inflammatory event depends on whether the primary demyelinating lesion is active or resolved.Brain Behav Immun. 2012 Jul.
Interleukin-1 β (IL-1β) is considered to be one of the most important
mediators in the pathogenesis of inflammatory diseases, particularly in
neurodegenerative diseases such as multiple sclerosis (MS). MS is a chronic inflammatory disease characterized by
demyelination and remyelination events, with unpredictable relapsing and
remitting episodes that seldom worsen MS lesions. We proposed to study
the effect of a unique component of the inflammatory process, IL-1β, and
evaluate its effect in repeated episodes, similar to the
relapsing-remitting MS pathology. Using adenoviral vectors, we developed
a model of focal demyelination/remyelination triggered by the chronic
expression of IL-1β. The long-term expression of IL-1β in the striatum
produced blood-brain barrier (BBB) breakdown, demyelination,
microglial/macrophage activation, and neutrophil infiltration but no
overt neuronal degeneration. This demyelinating process was followed by
complete remyelination of the area. This simple model allows us to study
demyelination and remyelination independently of the autoimmune and
adaptive immune components. Re-exposure to this cytokine when the first
inflammatory response was still unresolved generated a lesion with
decreased neuroinflammation, demyelination, axonal injury and glial
response. However, a second long-term expression of IL-1β when the first
lesion was resolved could not be differentiated from the first event.
In this study, we demonstrated that the response to a second
inflammatory stimulus varies depending on whether the initial lesion is
still active or has been resolved.
Interleukin-1 can do many things . This study used gene therapy to deliver the cytokine, adenoviral vectors produced transient but high levels of the cytokine. This triggered inflammationn and some demeylination which repairs. If it had repaired then another hit causes the same type of lesions but if the lesion had not remyelinated it decreased the inflammatory response so the response was not the same, therefore maybe treatments could have different effects depending on the lesion activity. This would be a cause for concern as lesions come and go at different times