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

Although interferon (IFN)-beta has shown a significant clinical benefit in multiple sclerosis (MS), its mechanism of action remains unclear. We found that IFN-P treatment of patients with MS resulted in a significant increase in apoptotic cell death (measured by annexin V staining and nuclear fragme ntation) of monocyte-derived macrophages, as compared with cells derived fr oth patients before treatment. Stimulation of the cells with IFN-P in vitro resulted in an even further increase of annexin V binding, as well as incr eased 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-P does not deliver a death signal to monocytes but rather primes for subsequent macrophage apoptosis upon activation or diffe rentiation.