Glatiramer acetate reduces lymphocyte proliferation and enhances IL-5 and IL-13 production through modulation of monocyte-derived dendritic cells in multiple sclerosis.
Dendritic cells (DC), as the most effective antigen presenting cells, are protagonists of the complex immune network involved in multiple sclerosis (MS) lesion formation. Glatiramer acetate (GA), a synthetic random copolymer, is thought to exert its therapeutical effect in MS by favouring both Th2 cell development and IL-10 production from peripheral lymphocytes as well as by systemically affecting the antigen presenting cells. In the present study we further analysed the mechanisms of action of GA by using an autologous DC-lymphocytes (Ly) coculture system from 11 MS patients and 12 matched healthy controls (HC). We found that, in MS patients, pretreatment with GA significantly decreases the in vitro proliferative effect of DC on lymphocytes as compared to HC and to unpulsed or myelin basic protein (MBP)-pulsed DC from MS patients (P < 0.05). In addition, GA-treated DC from both MS patients and HC significantly increase the lymphocyte production of IL-5 and IL-13 as compared to MBP-treated DC (P < 0.05). In conclusion our in vitro study may provide new therapeutical mechanisms of GA on lymphocytes, antiproliferative and Th2-favouring effects, which are mediated by monocyte-derived DC.
Sanna
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Institute of Clinical Neurology, University of Sassari, Italy. alexsan72@hotmail.com
Fois
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Arru
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Huang
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Link
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Pugliatti
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Rosati
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Sotgiu
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D000328:Adult; D002455:Cell Division / Q000276:immunology; D018920:Coculture Techniques; D003470:Culture Media; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000627:therapeutic use; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000276:immunology* / Q000627:therapeutic use
D003470:Culture Media; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D015848:Interleukin-5; D007378:Interleukins; D004676:Myelin Basic Protein; D010455:Peptides; D015847:Interleukin-4; D000068717:Glatiramer Acetate