Selective elimination of macrophages by dichlormethylene diphosphonate-containing liposomes suppresses experimental autoimmune neuritis.
The injection of liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP) constitutes an effective method to selectively eliminate phagocytic cells from spleen, liver and the circulation. We evaluated the effect of Cl2MDP-liposomes on the course of actively induced and adoptively transferred experimental autoimmune neuritis (EAN), both animal models of the human Guillain-Barré syndrome. Injection of Cl2MDP-liposomes 11 and 13 days postimmunization (p.i.) of Lewis rats with bovine peripheral nerve myelin efficiently prevented clinical signs of EAN up to day 15 p.i., when all control animals were affected. Thereafter, EAN gradually also developed in Cl2MDP-liposome-treated rats, but until day 19 disease was significantly milder than in control rats injected with buffer-filled liposomes. Adoptive transfer EAN (AT-EAN) induced by injection of activated P2-specific T cells could be suppressed even more markedly by application of Cl2MDP-liposomes 1, 3, and 6 days after cell transfer. Efficient suppression of AT-EAN by Cl2MDP-liposomes rules out the possibility that EAN is prevented due to interference with the induction phase of this experimental disease and confirms that macrophages are important effector cells during EAN. Selective suppression of phagocytic cell function by drug-containing liposomes may hold promise as a novel treatment of demyelinating autoimmune diseases of the nervous system.
Jung
S
S
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Huitinga
I
I
Schmidt
B
B
Zielasek
J
J
Dijkstra
C D
CD
Toyka
K V
KV
Hartung
H P
HP
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004002:Clodronic Acid / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects*; D009186:Myelin Sheath / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000523:psychology; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000473:pathology; D013126:Spinal Nerve Roots / Q000473:pathology
D008081:Liposomes; D004002:Clodronic Acid