麻豆果冻传媒影音

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 .

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 , 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.

They did detect IL4I1, and they found that treated cells had a decrease in gene expression for some pro-inflammatory cytokines, including IFNγ (P=0.02) and IL17 (P=0.04). They also saw increased expression for anti-proliferative proteins including TOB1 (P=0.02) and TGFβ (P=0.02).

Davis is also collecting data on patients with both active and non-active relapsing-remitting MS and secondary progressive MS, as well as other autoimmune conditions, to assess their IL4I1 status and how their cells react to treatment with IL4I1. She reported data on one patient with active relapsing-remitting MS, which generally were in line with findings in control cells, albeit to a different degree of magnitude.

"One interesting difference is that we see an increase in IFNγ, the pro-inflammatory cytokine, and increasing our sample will let us know if that's true," Davis said. "If it is, it could indicate that IL4I1 has different effects on the same cell types in people at different stages of MS."

Next steps for the team include using ELISA to check on protein production, rather than just assessing gene expression. But if IL4I1 proves to play a role in immune system modulation and remyelination, it could be a well-tolerated treatment, given that it's an endogenous protein, Davis said. It could also potentially be helpful in secondary progressive disease, for which there are currently no treatments.