Abstract Details

Title Interferon-? Induces Hepatocyte Growth Factor in Monocytes of Multiple Sclerosis Patients

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 160

Objective

Background BACKGROUND: The clinical benefit of IFN-? in RRMS is attributed to its immunomodulatory effects on inflammatory mediators and T cell reactivity. Recent data in mouse models of MS indicate that HGF alleviates EAE pathological inflammation and induces neuroprotective repair processes within the CNS (Benkhoucha M et al., PNAS, 2010; Bai L et al., Nat. Neurosci. 2012). In MS, cerebrospinal HGF levels correlate negatively with disease activity (Muller AM et al., J. Neuroimmunol. 2012). Thus, increasing HGF levels could represent one effective immunomodulatory and neuroprotective mechanisms of IFN-? in MS therapy.

Design/Methods DESIGN/METHODS: Expression of HGF in blood monocytes from RRMS patients treated (n=12) or not (n=15) with IFN-?-1a (Rebif®) was evaluated by intracellular flow cytometry analysis. Complementary in vitro studies addressed the mechanisms of HGF synthesis using enzyme-linked immunosorbent assay (ELISA), Western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) systems.

Results RESULTS: Here, we report that monocytes from RRMS patients exhibited a reduced ability to produce HGF when compared with healthy volunteers, and that monocytes from IFN-?-treated RRMS patients produced significantly higher levels of HGF (p<0.0001). In vitro studies further demonstrated that blood monocytes treated with IFN-? produce significant levels of HGF mRNA (qRT-PCR) and protein (WB, ELISA) and that IFN-? stimulated HGF production by both pro-inflammatory and classical monocyte subsets.

Conclusions CONCLUSIONS: Our data indicate that monocytes from untreated RRMS patients exhibit reduced HGF production compared with monocytes from IFN-?-treated RRMS patients. We confirmed that HGF production by blood monocytes is a direct effect of IFN-? treatment. Our findings thus suggest that IFN-? may mediate some of its therapeutic effects in RRMS through the induction of HGF by blood monocytes by coupling immune regulation and neuroprotection.

Authors/Disclosures
PRESENTER	No disclosure on file
Cynthia L. Harden, MD (Xenon Pharmaceuticals Inc)	Dr. Harden has received personal compensation for serving as an employee of Xenon Pharmaceuticals Inc.. Dr. Harden has stock in Xenon Pharmaceuticals Inc.. Dr. Harden has received intellectual property interests from a discovery or technology relating to health care.
Nicolas Molnarfi	No disclosure on file
	No disclosure on file
	No disclosure on file
Patrice LaLive, MD	Dr. LaLive has nothing to disclose.
Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.

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