High numbers of perforin mRNA expressing CSF cells in multiple sclerosis patients with gadolinium-enhancing brain MRI lesions.
Enhanced expression of pro- and anti-inflammatory cytokines is a common finding in MS, but attempts to correlate cytokine expression with disease activity have produced conflicting results. In this paper, gadolinium-(Gd-)enhancing lesions on brain MRI were used as markers for active inflammation in patients with MS not treated with any immunomodulatory drugs. In parallel, in situ hybridization was used to detect blood and cerebrospinal fluid (CSF) mononuclear cells (MNC) expressing cytokine mRNA. An association was observed between numbers of perforin mRNA expressing CSF MNC and numbers of Gd-enhancing brain MRI lesions. Perforin mRNA expressing CSF MNC were not detected in any of the patients lacking active lesions on brain MRI. The expression of tumor necrosis factor-alpha, interleukin-10 (IL-10) and IL-12 mRNA in CSF MNC did not differ between MS patients with and without active MRI lesions. Based on the present finding, a role for perforin in the disruption of the blood-brain barrier in MS can be hypothesized.
Division of Neurology, Karolinska Institutet, Huddinge University Hospital, Sweden.
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P
Kivisäkk
L
L
Stawiarz
D
D
Matusevicius
S
S
Fredrikson
M
M
Söderström
T
T
Hindmarsh
H
H
Link
D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D002556:Cerebrospinal Fluid Proteins / Q000235:genetics; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement; D017403:In Situ Hybridization / Q000379:methods; D016753:Interleukin-10 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D002556:Cerebrospinal Fluid Proteins; D003287:Contrast Media; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019786:Gadolinium DTPA