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Monocyte-derived IL12, CD86 (B7-2) and CD40L expression in relapsing and progressive multiple sclerosis
Lionel G Filion1, Darius Matusevicius, Gina M Graziani-Bowering
1Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada. lfilion@uottawa.ca
Clinical Immunology (Orlando, Fla.)
|April 4, 2003
Summary
Multiple sclerosis involves increased IL12 and costimulatory molecules like CD86 and CD40L in monocytes, particularly in progressive stages. Interferon-beta may reduce these markers, suggesting a therapeutic mechanism.
Area of Science:
- Immunology
- Neuroscience
Background:
- Multiple sclerosis (MS) is a T-helper 1 (Th1) autoimmune disease.
- Increased IFNgamma, IL12, and costimulatory molecules are implicated in MS pathogenesis.
Purpose of the Study:
- To investigate differential expression of IL12 and costimulatory molecules (CD80, CD86, CD28, CD40, CD40L) in monocytes and T cells.
- To compare these molecules in relapsing-remitting MS (RRMS) with and without IFNbeta treatment, secondary progressive MS (SPMS), and healthy controls (HC).
Main Methods:
- Cross-sectional and longitudinal flow cytometry studies on peripheral blood mononuclear cells (PBMC) and monocytes.
- In vitro culture with recombinant human IL10.
- Measurement of secreted IL12 levels.
Main Results:
- CD86 and CD40L expression on monocytes was highest in SPMS patients.
- IL10 reduced CD86 expression on RRMS monocytes more than on SPMS or HC monocytes.
- Monocytes from SPMS patients secreted over 10-fold more IL12 than RRMS or HC monocytes.
- IFNbeta-treated RRMS patients showed slightly lower IL12 secretion.
Conclusions:
- Increased CD86, CD40L expression, and IL12 production by monocytes are key in MS progression.
- IFNbeta may exert therapeutic effects by reducing monocyte CD86, CD40L, and IL12 levels.
- Failure of IFNbeta to reduce these markers may indicate treatment unresponsiveness or disease progression.