Quantitation of peripheral blood markers of rat experimental autoimmune encephalomyelitis.
Identification and quantitation of peripheral blood non-invasive, cell-surface markers of EAE disease activity and drug response would facilitate the preclinical development of potential therapeutics. Towards this end, we characterized the influx of immune mediators into spinal cords of diseased rats to establish the kinetics of T cell and monocyte-mediated inflammation. We then examined the periphery for regulation of T cell and monocyte activation. We report increased CD80 and VLA-4 expression on peripheral blood monocytes (PBM) during the onset and peak of experimental disease scores. Increased CD4+, CD62L - and CD4+, CD134+ T cells were detected only at disease peak, not during disease onset. PBM CD80 expression was significantly inhibited in CSA-treated animals, but increased in Dex-treated animals. PBM VLA-4 expression was unaffected by drug treatment. Both CSA and Dex inhibited CD62L shedding and CD134 expression on peripheral CD4+ T cells. These results identify quantitative, peripheral markers of disease activity and drug response.
Izmailova
Elena
E
The Inflammation Department and Molecular Medicine, Millennium Pharmaceuticals, Cambridge, MA 02139, USA. elena.izmailova@mpi.com
Walker
Russell
R
Fitzgerald
Michael
M
Ocain
Timothy
T
Jaffee
Bruce
B
Healy
Aileen M
AM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D016572:Cyclosporine / Q000276:immunology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D003907:Dexamethasone / Q000276:immunology / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D039041:Integrin alpha4beta1 / Q000097:blood* / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D051381:Rats; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents; D039041:Integrin alpha4beta1; D003907:Dexamethasone; D016572:Cyclosporine