title: Interleukin-12 and perforin mRNA expression is augmented in blood mononuclear cells in multiple sclerosis.
abstract: 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.
authors.affiliation: Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Darius.Matusevicius@cnsf.ki.se
authors.forename: D
authors.initials: D
authors.lastname: Matusevicius
authors.forename: P
authors.initials: P
authors.lastname: Kivisäkk
authors.forename: V
authors.initials: V
authors.lastname: Navikas
authors.forename: M
authors.initials: M
authors.lastname: Söderström
authors.forename: S
authors.initials: S
authors.lastname: Fredrikson
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: 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
chemical_list: D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D018664:Interleukin-12