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Suppression of experimental allergic encephalomyelitis in Lewis rats treated with myelin basic protein-liposome
Abstract:
Guinea pig myelin basic protein (MBP) was inserted into phosphatidylserine liposomes and Lewis rats were injected by the intracardiac (ic) route with 75 microgram doses of MBP-liposomes according to various schedules. After challenge with 75 microgram guinea pig MBP in complete Freund's adjuvant, the rats were followed for clinical signs, were tested for delayed hypersensitivity (DTH) and lymphocyte transformation (LT) to MBP. The animals were sacrificed 30 days after challenge and the central nervous system tissue was examined for histological modifications. Rats treated with two injections of MBP-liposomes, 7 days before and 7 days after challenge, showed the highest degree of protection from clinical manifestations. Histological lesions were not significantly reduced. DTH reactions to MBP were all positive, regardless of treatment. LT assays were positive overall in only 50% of the animals tested. The response to rat MBP was significantly lower than to guinea pig MBP, especially in the groups treated with MBP-liposomes. Adoptive transfer of spleen cells from MBP-liposome-treated donors reduced the clinical scores of actively induced EAE in syngeneic recipients by 40-50%. These results suggest that at least one mechanism responsible for antigen-specific protection in EAE by MBP-liposomes operates through active suppression transferable by spleen cells.
Insights
Liposome-encapsulated myelin basic protein (MBP) shows promise in protecting rats against experimental autoimmune encephalomyelitis (EAE). This treatment may involve active suppression transferable by spleen cells, offering a potential therapeutic avenue for EAE.
Area of Science:
- Neuroimmunology
- Immunotherapy
- Liposome technology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis.
- Myelin basic protein (MBP) is a key autoantigen in EAE.
- Liposomes are used as drug delivery vehicles for immunotherapy.
Purpose of the Study:
- To investigate the efficacy of guinea pig myelin basic protein (MBP) encapsulated in liposomes for preventing EAE in Lewis rats.
- To explore the immunological mechanisms underlying MBP-liposome mediated protection.
Main Methods:
- Lewis rats were injected with MBP-liposomes via the intracardiac route at various schedules.
- Rats were challenged with guinea pig MBP in complete Freund's adjuvant.
- Clinical signs, delayed hypersensitivity (DTH), lymphocyte transformation (LT), and central nervous system histology were assessed.
- Adoptive transfer experiments were conducted using spleen cells from treated donors.
Main Results:
- Two injections of MBP-liposomes before and after challenge provided the highest protection against clinical EAE manifestations.
- Histological lesions were not significantly reduced by the treatment.
- DTH reactions were uniformly positive, while LT assays showed positive responses in only 50% of animals.
- Adoptive transfer of spleen cells from MBP-liposome-treated donors reduced clinical scores by 40-50%.
Conclusions:
- MBP-liposomes demonstrate significant protection against clinical EAE, suggesting a therapeutic potential.
- The protective mechanism appears to involve active suppression transferable by spleen cells.
- Further research is warranted to elucidate the precise immunomodulatory effects of MBP-liposomes in EAE.