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