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

J Neuroimmunol. 2000 Sep 22;109(2):105-11. doi: 10.1016/s0165-5728(00)00279-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Benzodiazepines / metabolism
  • Binding Sites / immunology
  • C-Reactive Protein / genetics*
  • Dexamethasone / pharmacology*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Glucocorticoids / pharmacology*
  • Interleukin-6 / immunology*
  • Isoquinolines / metabolism
  • Isoquinolines / pharmacology
  • Kinetics
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Phosphodiesterase Inhibitors / pharmacology*
  • RNA, Messenger / analysis
  • Radioligand Assay
  • Rats
  • Rats, Inbred Lew
  • Receptors, GABA-A / chemistry
  • Receptors, GABA-A / immunology
  • Receptors, GABA-A / metabolism
  • Rolipram / pharmacology*
  • Serum Amyloid P-Component / genetics*
  • Spinal Cord / drug effects
  • Spinal Cord / immunology*
  • Tritium
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antineoplastic Agents
  • Glucocorticoids
  • Interleukin-6
  • Isoquinolines
  • Phosphodiesterase Inhibitors
  • RNA, Messenger
  • Receptors, GABA-A
  • Serum Amyloid P-Component
  • Tumor Necrosis Factor-alpha
  • Tritium
  • Benzodiazepines
  • PTX3 protein
  • Dexamethasone
  • C-Reactive Protein
  • Rolipram
  • PK 11195