Immunomodulatory effects of interferon beta-1a in multiple sclerosis.
Several studies have established a role for interferon beta (IFNbeta) as a treatment for relapsing-remitting multiple sclerosis (MS). IFNbeta 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 IFNbeta may underlie its clinical efficacy. We used intracellular cytokine flow cytometry to analyze the effects of IFNbeta-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 IFNbeta-1a. The primary cellular sources of IL-10 were monocytes and CD4(+) T lymphocytes. IL-10 production in response to IFNbeta-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 IFNbeta-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 IFNbeta-1a treatment of MS patients. IFNbeta-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 IFNbeta-1a treatment. These data suggest that co-stimulatory molecules are modulated by IFNbeta, providing a possible mechanism for its in vivo immune regulatory effects.
Liu
Z
Z
Department of Neurosciences, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Pelfrey
C M
CM
Cotleur
A
A
Lee
J C
JC
Rudick
R A
RA
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D023201:CD40 Ligand / Q000096:biosynthesis; D002478:Cells, Cultured; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D023201:CD40 Ligand; D016899:Interferon-beta; D000068556:Interferon beta-1a