title: Peripheral levels of caspase-1 mRNA correlate with disease activity in patients with multiple sclerosis; a preliminary study.
abstract: The cysteine protease caspase-1 plays a crucial part in the inflammatory process due to its ability to proteolitically activate proinflammatory cytokine precursors, such as interleukin (IL)-1beta and IL-18. Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS in which the pathogenic process is mainly orchestrated by proinflammatory cytokines. The role of caspase-1 in multiple sclerosis was evaluated by measuring its mRNA levels in peripheral blood mononuclear cells (PBMCs) from seven patients with relapsing-remitting multiple sclerosis every 15 days over a 1 year period. The recorded levels were compared with clinical and MRI evidence of disease activity. Brain MRI was performed monthly in each patient. Caspase-1 mRNA levels were significantly increased in PBMCs from patients with multiple sclerosis compared with healthy controls (p<0.001). In patients with multiple sclerosis, a twofold to threefold increase of caspase-1 mRNA mean level was found in the week preceding an acute attack (p<0. 05). The magnitude of caspase-1 mRNA increase correlated with the number of new (p=0.01) but not persisting gadolinium enhancing brain MRI lesions. In conclusion, caspase-1 might be involved in the immune mediated process underlying CNS inflammation and might represent a suitable peripheral immunological marker of disease activity in multiple sclerosis.
authors.affiliation: Experimental Neuroimmunotherapy Unit, Department of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Furlan
authors.forename: M
authors.initials: M
authors.lastname: Filippi
authors.forename: A
authors.initials: A
authors.lastname: Bergami
authors.forename: M A
authors.initials: MA
authors.lastname: Rocca
authors.forename: V
authors.initials: V
authors.lastname: Martinelli
authors.forename: P L
authors.initials: PL
authors.lastname: Poliani
authors.forename: L M
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: G
authors.initials: G
authors.lastname: Desina
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: G
authors.initials: G
authors.lastname: Martino
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D020170:Caspase 1 / Q000235:genetics* / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index
chemical_list: D018076:DNA, Complementary; D005819:Genetic Markers; D007375:Interleukin-1; D020382:Interleukin-18; D011498:Protein Precursors; D012333:RNA, Messenger; D020170:Caspase 1