Early work suggests beneficial effect of IL4I1 in multiple sclerosis
by Kristina Fiore, Deputy Managing Editor, MedPage TodayNovember 13, 2017
WASHINGTON — A cytokine-related protein may be a marker of disease severity in multiple sclerosis, and may eventually prove to be a remyelinating therapeutic agent, researchers reported here.
In a small proof-of-concept study, interleukin-4 induced protein 1 (IL4I1) was detected in human peripheral blood mononuclear cells, and adding more of it to those cells in vitro tamped down levels of two key pro-inflammatory cytokines thought to be drivers of MS: interferon-gamma (IFNγ) and IL17, according to Stephanie Davis, an MD/PhD candidate at Georgetown University.
“This is telling us, just as we saw in mice, that even in humans, IL4I1 can have an immune-modulating effect,” Davis told MedPage Today during a poster session at the Society for Neuroscience meeting here.
IL4I1 is a secreted L-amino acid oxidase expressed by immune cells. Its exact function isn’t clear, and it has rarely been studied in the context of the central nervous system, but it does play a role in phenylalanine metabolism, Davis said.
The protein first appeared on her team’s radar — she works at Georgetown’s Huang Lab — in a microarray analysis of genes expressed from demyelination to remyelination in a rat model. IL4I1 was highly upregulated at the onset of remyelination, they found.
Subsequent work showed that treatment with IL4I1 diminished inflammation and boosted remyelination in molecular models of MS in mice, and behavioral mouse models showed a reduction in symptoms in treated animals.
To assess whether IL4I1 is detectable in human cells, Davis and colleagues assessed peripheral blood mononuclear cells in vitro. Cells were stimulated to isolate the T cell component, then the researchers added either IL4I1 or a saline control to assess effects on gene expression.
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