Immunomodulatory effects of interferon beta-1a in multiple sclerosis

• Published in: Journal of neuroimmunology Vol. 112; no. 1; pp. 153 - 162
• Main Authors: Liu, Zhugong, Pelfrey, Clara M., Cotleur, Anne, Lee, Jar-Chi, Rudick, Richard A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 2001
• Subjects: Antigens, CD - biosynthesis; b-Interferon; B7-1 Antigen - biosynthesis; B7-2 Antigen; CD40 Ligand - biosynthesis; Cells, Cultured; Co-stimulatory molecules; Humans; IFN-beta; IL-10; Interferon beta-1a; Interferon-beta - therapeutic use; Interleukin-10 - biosynthesis; Leukocytes, Mononuclear - metabolism; Membrane Glycoproteins - biosynthesis; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; IFN-beta; Multiple sclerosis; Co-stimulatory molecules; IL-10
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(00)00403-3

Several studies have established a role for interferon beta (IFNβ) as a treatment for relapsing–remitting multiple sclerosis (MS). IFNβ has been reported to decrease the relapse rate, relapse severity, progression of disability and development of new brain lesions. Its mechanisms of action, however, remain unclear. We hypothesize that immunomodulatory effects of IFNβ may underlie its clinical efficacy. We used intracellular cytokine flow cytometry to analyze the effects of IFNβ-1a on expression of the anti-inflammatory cytokine, IL-10, and its effects on major co-stimulatory molecules in MS patients. We found that peripheral blood mononuclear cells (PBMC) produced more IL-10 following in vitro or in vivo treatment with IFNβ-1a. The primary cellular sources of IL-10 were monocytes and CD4 + T lymphocytes. IL-10 production in response to IFNβ-1a was increased in unseparated PBMC compared to purified lymphocyte cultures, indicating that interaction between monocytes and lymphocytes may influence IL-10 production in response to IFNβ-1a. Using flow cytometry, we monitored the ex vivo expression of two major co-stimulatory pairs-B7/CD28 and CD40/CD40L-before and after intramuscular IFNβ-1a treatment of MS patients. IFNβ-1a lowered the expression of B7.1 on circulating B cells and increased B7.2 expression on monocytes. CD40 expression on B cells was down-regulated, but CD40 on monocytes was up-regulated by IFNβ-1a treatment. These data suggest that co-stimulatory molecules are modulated by IFNβ, providing a possible mechanism for its in vivo immune regulatory effects.