Decreased levels of CD95 and caspase-8 mRNA in multiple sclerosis patients with gadolinium-enhancing lesions on MRI

Magnetic resonance imaging (MRI) allows examining inflammation and central nervous system (CNS) tissue damage in patients suffering from multiple sclerosis (MS), a demyelinating disease of the CNS. Using real-time PCR, we quantified mRNA levels of apoptosis regulators CD95, CD95 ligand, caspase-8, -10 and cellular FLICE-inhibitory protein (cFLIP), and cytokines IL-10 and TNF-alpha in blood mononuclear cells of MS patients at the time of MRI examination. Patients with detectable gadolinium-enhancing lesions had lower expression of CD95 and caspase-8 (P < 0.05). Lesion load and brain atrophy did not correlate with expression levels of any of the target molecules studied. Disease duration correlated positively with both FLIP/caspase-8 and CD95/CD3 ratios (P < 0.05). These results support the notion that the CD95-dependent pathway plays a complex role in the regulation of survival of activated immune cells in MS. (C) 2003 Elsevier Ireland Ltd. All rights reserved.