In-situ expression of Interleukin-18 and associated mediators in the human brain of sALS patients: Hypothesis for a role for immune-inflammatory mechanisms
Section snippets
Introduction/background
Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly progressing condition.
It is one of the severest neurodegenerative diseases that involves upper- and lower motor neurons, with typical limbs-, trunk-, and bulbar involvement, causing death usually from neurogenic muscle weakness. Many cases, besides, show or evolve with a distinctive component, namely fronto-temporal atrophy and/or dementia (FTD); a clinico-pathological spectrum of ALS/FTD has thus emerged [1], [2], and insights
The hypothesis
Growing evidence on the implication of proinflammatory cytokines in cerebral neuronal dysfunction and cell death in several neurological disorders (such as multiple sclerosis, Alzheimer’s dementia, Parkinson, and others…), together with the recent reporting of overexpression of IL-18 (a known inflammatory cytokine) in the sera of patients with sALS [13], prompted us to hypothesize that this cytokine (IL-18) could take part in physiopathological mechanisms underlying cerebral neuronal
Evaluation of the hypothesis
In order to find out if IL-18 could possibly be implicated in neural cell injury/damage particularly in the brain, it was imperative to verify and explore whether this cytokine (IL-18) and eventually related molecules, were actually present and expressed within the brain itself.
Empirical data/supportive results
To that aim, we carried-out a retrospective neuropathological study to explore sALS brains for eventual expression of IL-18 cytokine in cerebral tissue, and to see if related immune-inflammatory mediators/network were activated in the CNS of sALS patients.
We explored archived paraffin-embedded tissue-blocks from four human brains for the eventual presence of the IL-18 cytokine (in brain tissues), and we also looked for key-mediators closely related to IL-18, namely RIP3, caspase-1 and the
Discussion
Our empirical data presented herein provide first evidence on the detection of in-situ expression of activated IL-18 in the human brain in sALS patients. Interestingly, overexpression of IL-18 has been recently observed in the sera of sALS patients [13].
In this observational study, we also detected the cerebral in-situ expression/activation of key-molecules that are known to be closely related to the molecular network associated with IL-18 cytokine production/activation, namely, RIP3,
Conflict of interest statement
None.
Acknowledgements
Authors thank Mr. Abderahmane Bouysantiman and Mr. Jean-Yves Bonnet (Belgium), and Mr. Djordie Grbic and Mrs. Clémence Guiraut (Canada) for excellent technical assistance. Research-financing (HK) was provided by “Fondation Brugmann” at CHU-BRUGMANN (a non-profit University-Hospital Funding Body).
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