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Selective elimination of macrophages by dichlormethylene diphosphonate-containing liposomes suppresses experimental
S Jung1, I Huitinga, B Schmidt
1Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Abstract:
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.
Insights
Liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP) effectively reduced experimental autoimmune neuritis (EAN) in rats by eliminating phagocytic cells. This targeted approach shows promise for treating demyelinating autoimmune diseases.
Area of Science:
- Neuroimmunology
- Pharmacology
- Cell Biology
Background:
- Experimental autoimmune neuritis (EAN) is an animal model for Guillain-Barré syndrome.
- Phagocytic cells, particularly macrophages, play a role in autoimmune nerve damage.
Purpose of the Study:
- To investigate the therapeutic potential of liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP-liposomes) in EAN models.
- To determine the role of phagocytic cells in the pathogenesis of EAN.
Main Methods:
- Administration of Cl2MDP-liposomes to Lewis rats immunized with myelin to induce EAN.
- Adoptive transfer of P2-specific T cells to induce EAN (AT-EAN).
- Evaluation of clinical signs and disease severity in treated versus control groups.
Main Results:
- Cl2MDP-liposomes significantly delayed and reduced clinical signs of actively induced EAN.
- Treatment with Cl2MDP-liposomes markedly suppressed AT-EAN, even when administered after T cell transfer.
- These findings confirm the crucial role of macrophages as effector cells in EAN.
Conclusions:
- Selective elimination of phagocytic cells using Cl2MDP-liposomes is an effective strategy for managing EAN.
- This approach offers a potential novel therapeutic avenue for demyelinating autoimmune disorders of the nervous system.