Interleukin-12 and perforin mRNA expression is augmented in blood mononuclear cells in multiple sclerosis.
Cytokines are suggested to orchestrate an abnormal immune response in multiple sclerosis (MS). The regulatory cytokine interleukin (IL)-12 induces T-helper (Th) cell switch to the Th1 type and the production by cytotoxic T cells of perforin, a cell lysis-inducing factor. It has been suggested that Th1-like cytokines may promote the development of MS, and the production of perforin to induce oligodendrocyte damage. In-situ hybridization with radiolabelled synthetic oligonucleotide probes was used to detect and enumerate mononuclear cells (MNC) expressing IL-12 and perforin mRNA in blood and cerebrospinal fluid (CSF) from patients with MS and controls. Plasma and CSF levels of IL-12 (p70) were evaluated by ELISA. Higher numbers of IL-12 and perforin mRNA-expressing MNC were registered in blood in MS and also in controls with aseptic meningoencephalitis (AM) compared to healthy subjects. There were a few patients with other non-inflammatory neurological diseases who also had high levels of IL-12 or perforin mRNA expressing blood MNC. A parallel elevation was observed for IL-12 (p70) concentrations in plasma. In the MS patients' CSF, there was a further augmentation of IL-12 mRNA expressing MNC. To evaluate autoantigen-induced IL-12 and perforin mRNA expression, blood MNC were cultivated +/- myelin basic protein (MBP), a candidate autoantigen in MS. Higher numbers of MBP-reactive IL-12 and perforin mRNA expressing blood MNC were detected in MS than controls. The augmentation of both IL-12 and perforin in MS might reflect ongoing inflammatory processes in MS and could represent targets for future treatments.
Matusevicius
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Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Darius.Matusevicius@cnsf.ki.se
Kivisäkk
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Navikas
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Söderström
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Fredrikson
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Link
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger
D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D018664:Interleukin-12