Treatment of multiple sclerosis patients with interferon-beta primes monocyte-derived macrophages for apoptotic cell death

Abstract

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-03-24T17:46:43Z No. of bitstreams: 1 Van Weyenbergh J Treatment of multiple....pdf: 177035 bytes, checksum: e34a48be36ad1034ddfea20d2289a1d4 (MD5)Made available in DSpace on 2014-03-24T17:46:43Z (GMT). No. of bitstreams: 1 Van Weyenbergh J Treatment of multiple....pdf: 177035 bytes, checksum: e34a48be36ad1034ddfea20d2289a1d4 (MD5) Previous issue date: 2001INSERM. Paris, FrançaINSERM. Paris, FrançaInstitut Curie. Section de Recherche. Paris, FrançaFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilAlthough interferon (IFN)-b has shown a significant clinical benefit in multiple sclerosis (MS), its mechanism of action remains unclear. We found that IFN-b treatment of patients with MS resulted in a significant increase in apoptotic cell death (measured by annexin V staining and nuclear fragmentation) of monocyte-derived macrophages, as compared with cells derived from patients before treatment. Stimulation of the cells with IFN-b in vitro resulted in an even further increase of annexin V binding, as well as increased Fas (CD 95, APO-1) expression. However, no increased Fas expression, apoptotic monocytes, or monocytopenia were observed upon in vivo treatment. This indicates that IFN-b does not deliver a death signal to monocytes but rather primes for subsequent macrophage apoptosis upon activation or differentiatio