Interferon-β Induces Hepatocyte Growth Factor in Monocytes of Multiple Sclerosis Patients (P05.160)

OBJECTIVE: To evaluate the production of hepatocyte growth factor (HGF) by peripheral blood monocytes from relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon (IFN)-β. BACKGROUND: The clinical benefit of IFN-β 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-β in MS therapy. DESIGN/METHODS: Expression of HGF in blood monocytes from RRMS patients treated (n=12) or not (n=15) with IFN-β-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: 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-β-treated RRMS patients produced significantly higher levels of HGF (p CONCLUSIONS: Our data indicate that monocytes from untreated RRMS patients exhibit reduced HGF production compared with monocytes from IFN-β-treated RRMS patients. We confirmed that HGF production by blood monocytes is a direct effect of IFN-β treatment. Our findings thus suggest that IFN-β may mediate some of its therapeutic effects in RRMS through the induction of HGF by blood monocytes by coupling immune regulation and neuroprotection. Supported by: Swiss National Foundation (#310030–132705 to P.H.L) and the Swiss Multiple Sclerosis Society (to P.H.L. and N.M.). N.M. is a recipient of an ECTRIMS fellowship exchange programme. Disclosure: Dr. Benkhoucha has nothing to disclose. Dr. Molnarfi has nothing to disclose. Dr. Bjarnadottir has nothing to disclose. Dr. Juillard has nothing to disclose. Dr. Lalive received honoraria for speaking from Biogen-Idec, Merck Serono, Novartis, Sanofi-Aventis, Teva; has received consulting fees from Biogen-Idec, Geneuro, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, Teva. Dr. Lalive has received financial support for research activities from Biogen-Idec, Merck Serono, Novartis.