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Effect of cyclosporine on rubella virus-specific immune responses in chronic progressive multiple sclerosis
A Nath1, J S Wolinsky, R H Kerman
1Department of Neurology, University of Texas Health Science Center, Houston.
Abstract:
Cyclosporine A (CsA) has been used in putative autoimmune diseases after sensitization to unknown antigens. We have previously shown that CsA prevented continued activation of T-cells in chronic progressive multiple sclerosis (CPMS) patients. The current study was undertaken to determine whether CsA, or CsA and prednisone (CsA + P) could suppress immune responses to a common recall antigen. Serum antibody levels were higher in all CPMS patients than age-matched normal controls. However, rubella antibody titers in the CsA or CsA + P groups were no different from a placebo-treated CPMS patient group. The lymphocyte responses to inactivated rubella virus of CsA and CsA + P-treated CPMS patients were lower than placebo and control but not statistically different. Therapy with both CSA and CSA + P was associated with significantly lower panel mixed leukocyte responses and Ta1 expression than in the placebo-treated group; CD3, CD4, CD8 antigen expression and active rosette formation by T-cells were similar for the three CPMS groups. These results suggest that while CsA exerts measurable effects on non-specific indicators of cellular immunity in CPMS patients, it may not be as effective in suppressing pre-existent specific immune responses.
Insights
Cyclosporine A (CsA) and prednisone (CsA + P) showed limited effectiveness in suppressing specific immune responses to recall antigens in chronic progressive multiple sclerosis (CPMS) patients. While CsA impacted non-specific cellular immunity indicators, pre-existing immune responses remained largely unaffected.
Area of Science:
- Immunology
- Neuroimmunology
- Pharmacology
Background:
- Cyclosporine A (CsA) is used in autoimmune diseases.
- Previous research indicated CsA prevents T-cell activation in chronic progressive multiple sclerosis (CPMS).
- CPMS patients exhibit higher serum antibody levels than healthy controls.
Purpose of the Study:
- To evaluate the efficacy of CsA, and CsA with prednisone (CsA + P), in suppressing immune responses to a common recall antigen in CPMS patients.
- To assess the impact of CsA and CsA + P on specific and non-specific immune markers.
Main Methods:
- CPMS patients were treated with CsA, CsA + P, or placebo.
- Serum antibody titers (rubella) and lymphocyte responses to inactivated rubella virus were measured.
- Panel mixed leukocyte responses, T-cell antigen expression (CD3, CD4, CD8), and active rosette formation were assessed.
Main Results:
- Rubella antibody titers and lymphocyte responses to rubella virus did not differ significantly between CsA/CsA + P groups and placebo.
- CsA and CsA + P treatments significantly reduced panel mixed leukocyte responses and Ta1 expression compared to placebo.
- CD3, CD4, CD8 antigen expression and T-cell active rosette formation were similar across all CPMS groups.
Conclusions:
- CsA demonstrates measurable effects on non-specific cellular immunity indicators in CPMS patients.
- CsA and CsA + P may not effectively suppress pre-existent specific immune responses to recall antigens in CPMS.
- Further research is needed to clarify the role of CsA in managing CPMS-related immune dysregulation.