title: Increased peripheral benzodiazepine binding sites and pentraxin 3 expression in the spinal cord during EAE: relation to inflammatory cytokines and modulation by dexamethasone and rolipram.
abstract: We have studied the mRNA expression of pentraxin 3 (PTX3) and the binding of the peripheral-type benzodiazepine receptor (PBR) ligand, [3H]-PK11195, in the spinal cord of Lewis rats where EAE was actively induced. PTX3 was induced during the active phase of EAE (day 10-14), it remained high up to 30 days and disappeared only 60 days later. Similarly, PK11195 binding peaked at day 14-17 during the recovery and it disappeared by day 60. On the other hand, the levels of TNF and IL-6 in the spinal cord were elevated at the peak and at the onset of clinical signs and returned to non-detectable by day 14-17. Dexamethasone abolished all these changes, while treatment with rolipram, delayed the appearance of the disease and then decreased its severity. However the peaks of TNF, IL-6, PBR and PTX3 levels in spinal cord were only delayed, but not reduced, by rolipram treatment. In conclusion, we show two types of inflammatory changes in EAE: acute, short term changes (TNF and IL-6), that correlate with the disease; and effects such as PTX3 expression and PK11195 binding that last longer after recovery from the disease.
authors.affiliation: 'Mario Negri' Institute for Pharmacological Research, Milano, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Agnello
authors.forename: L
authors.initials: L
authors.lastname: Carvelli
authors.forename: V
authors.initials: V
authors.lastname: Muzio
authors.forename: P
authors.initials: P
authors.lastname: Villa
authors.forename: B
authors.initials: B
authors.lastname: Bottazzi
authors.forename: N
authors.initials: N
authors.lastname: Polentarutti
authors.forename: T
authors.initials: T
authors.lastname: Mennini
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001569:Benzodiazepines / Q000378:metabolism; D001665:Binding Sites / Q000276:immunology; D002097:C-Reactive Protein / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology*; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D051381:Rats; D011917:Rats, Inbred Lew; D011963:Receptors, GABA-A / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D020889:Rolipram / Q000494:pharmacology*; D000683:Serum Amyloid P-Component / Q000235:genetics*; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology*; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000099153:Pentraxins
chemical_list: D000970:Antineoplastic Agents; D001569:Benzodiazepines; D002097:C-Reactive Protein; D003907:Dexamethasone; D005938:Glucocorticoids; D015850:Interleukin-6; D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D020889:Rolipram; D000683:Serum Amyloid P-Component; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha; D000099153:Pentraxins; C037850:PK 11195