title: IVIG enters the central nervous system during treatment of experimental autoimmune encephalomyelitis and is localised to inflammatory lesions.
abstract: Intravenous immunoglobulin (IVIG) treatment reduces the relapse rate in relapsing-remitting multiple sclerosis (MS) and may interfere with MS pathology through its various anti-inflammatory and immunomodulatory properties. It is presently unknown whether IVIG enters the central nervous system (CNS) in sufficient amounts to influence the local immune response within the brain and spinal cord, or if the treatment effects are entirely due to peripheral actions of IVIG. The purpose of the present study was to evaluate if IVIG radiolabeled with 99mTc enters the CNS during treatment of experimental autoimmune encephalomyelitis (EAE) in the susceptible rat strain Dark Agouti. After in vivo administration of 99mTc-IVIG we observed significantly increased accumulation in the brain and spinal cord from rats with EAE. Accumulation of 99mTc-IVIG was not detectable in CNS tissue from control animals. In peripheral tissue samples minor increases in 99mTc-IVIG organ binding were observed in the liver and kidney during EAE. Localisation of 99mTc-IVIG in the brain tissue was visualised by autoradiography and revealed significant accumulation of IVIG only in areas also affected by perivascular inflammation and leakage of serum proteins. In conclusion, the results indicate that significant extravasation of IVIG to the CNS only occurs when blood-brain barrier function is compromised during EAE.
authors.affiliation: Danish MS Research Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet sect. 6311, 2100 Copenhagen, Denmar. shj@astion.com
authors.forename: Signe Humle
authors.initials: SH
authors.lastname: Jorgensen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Storm
authors.forename: Poul Erik Hyldgaard
authors.initials: PE
authors.lastname: Jensen
authors.forename: Henning
authors.initials: H
authors.lastname: Laursen
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sorensen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016756:Immunoglobulins, Intravenous / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008297:Male; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D019275:Radiopharmaceuticals