Combination treatment of Glatiramer Acetate and Minocycline affects phenotype expression of blood monocyte-derived dendritic cells in Multiple Sclerosis patients.
The effects of Glatiramer Acetate (GA) in combination with Minocycline (MIN), a second-generation tetracycline, have been investigated on the course of EAE in mice, resulting in a significant reduction in disease severity and burden with attenuation of the inflammation, axonal loss and demyelination. Here we investigate the effects of combination therapy with GA and MIN on the induction, maturation and phenotyping of blood monocyte-derived dendritic cells (DCs) in Multiple Sclerosis (MS) patients. Hence the expressions of HLA-DR, CD11c, CD83 and CD1a were studied by flow cytometric analysis on immature (iDCs) and mature DCs (mDCs) from untreated and GA treated MS patients. Thirteen relapsing-remitting MS patients and 13 healthy controls (HCs) were included in the study. Ten of the MS patient group were re-tested after a 2 month period of GA treatment. The marker expressions on DC from untreated MS and HCs were studied in vitro in the absence or presence of GA and GA+MIN; and on DCs from GA treated MS patients without and with the in vitro addition of MIN. We found that in vitro GA alone or in combination with MIN downregulated DCs antigen presentation capability (HLA-DR), whereas the combination treatment only affected also myeloid DCs activation (CD83) in both MS and HCs. Prolonged GA treatment (in vivo for 2 months) affected antigen presentation capability by DCs, whereas when treated in vitro with MIN these cells also tended to reduce activation marker expression and myeloid phenotype acquisition (CD11c). The present data demonstrate possible combination effects of GA and MIN on peripheral blood monocyte-derived DCs in MS patients.
Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy.
Maddalena
M
Ruggieri
Carmela
C
Pica
Anna
A
Lia
Giovanni B
GB
Zimatore
Mattea
M
Modesto
Emilia
E
Di Liddo
Luigi M
LM
Specchio
Paolo
P
Livrea
Maria
M
Trojano
Carlo
C
Avolio
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D000068717:Glatiramer Acetate; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008911:Minocycline / Q000494:pharmacology*; D009103:Multiple Sclerosis / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D004338:Drug Combinations; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D008911:Minocycline