Regulation of differentiation and functional properties of monocytes and monocyte-derived dendritic cells by interferon beta in multiple sclerosis

• Published in: Multiple sclerosis Vol. 10; no. 5; pp. 499 - 506
• Main Authors: Zang, Ying CQ, Skinner, Sheri M, Robinson, Rachel R, Li, Sufang, Rivera, Victor M, Hutton, George J, Zhang, Jingwu Z
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01.10.2004; Arnold; Sage Publications Ltd
• Subjects: Adjuvants, Immunologic - administration & dosage; Adult; Biological and medical sciences; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cells, Cultured; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Humans; Immunomodulators; Immunophenotyping; Interferon beta-1a; Interferon-beta - administration & dosage; Interleukin-1 - metabolism; Medical sciences; Middle Aged; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Chronic Progressive - drug therapy; Multiple Sclerosis, Chronic Progressive - immunology; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Neurology; Pharmacology. Drug treatments; Tumor Necrosis Factor-alpha - metabolism; interferon beta; multiple sclerosis; dendritic cells; Dendritic cell; Multiple sclerosis; Nervous system diseases; Monocyte; Central nervous system disease; Beta interferon; Degenerative disease; Inflammatory disease
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1191/1352458504ms1081oa

Interferon beta (IFN beta) has complex immune regulatory properties that contribute to its treatment effect on multiple sclerosis (MS). In this study, we investigated the role of IFN beta in differentiation and functional properties of monocytes and monocyte-derived dendritic cells that are critical to the inflammatory process in MS. The results revealed that IFN beta inhibited intracellular production of interleukin (IL)-1b (PB/0.01) in both monocytes exposed toin vitro treatment of IFN beta and monocytes analysedex vivo from MS patients treated with IFN beta. IFN beta was shown to modulate differentiation of monocytes into dendritic cells in the presence of IL-4 and GM-CSF, which resulted in a delayed differentiation process. Furthermore, it characteristically altered the phenotypic features of differentiated dendritic cells by inhibiting the expression of CD1a, CD11b, CD11c, CD123 and CD209 while upregulating costimulatory molecules, such as CD86. The selective regulatory properties of IFN beta appeared to render the function of differentiated dendritic cells to produce an increased amount (PB/0.01) while their ability to secrete proinflammatory IL-12 and TGF beta was significantly reduced. The observed collective effects of IFN beta seemed to correlate with Th2 immune deviation. The study has provided new insights into the regulatory mechanisms of IFN beta in the treatment of MS.