IFN-γ, IFN-β, and PGE Affect Monokine Secretion: Relevance to Monocyte Activation in Multiple Sclerosis

Effects of cytokines on microglial phenotypes and astroglial coupling in an inflammatory coculture model

“…Second, we monitored the astrocytic membrane resting potential of plasma membrane activity. The following pro-and antiinflammatory molecules, which have been shown to convey potent effects on CNS inflammatory reactions, were applied to the culture system: (1) TNF-a, which is preferentially produced by cells of the macrophage lineage including microglia, and known to be one of the most active proinflammatory mediators under a variety of inflammatory conditions (Larrick andWright 1990, Chabot et al, 1997); (2) IL-1b, which plays an important role in initiating immune responses and has been found to activate lymphocytes and microglia (Dinarello, 1991); (3) IL-6, which exerts proinflammatory activity like acute-phase responses and B-cell stimulation, but also possesses antiinflammatory characteristics, such as restraining the inflammatory and demyelinating processes in MS (Stelmasiak et al, 2001); (4) the proinflammatory cytokine IFN-g, which is secreted by macrophages and activated T lymphocytes in MS lesions, where its level of secretion correlates with the disability status of MS patients (Petereit et al, 2000); it also induces class II MHC antigen expression in monocytes and astrocytes (Porrini and Reder 1994); (5) two antiinflammatory substances TGF-b1 and IFN-b. TGF-b1, besides its multiple effect on T-cell suppression, MHC class II downregulation and deactivation of macrophages (Hailer et al, 1998) has been found to exert a robust downregulation of the production of proinflammatory cytokines in the brain (Khoury et al, 1992), while IFN-b has been proved to promote the secretion of endogenous antiinflammatory cytokines like TGF-b1 and IL-10 (Porrini et al, 1995;Ossege et al, 1999).…”

Cloning and expression of murine IFNβ and a TNF antagonist for gene therapy of experimental allergic encephalomyelitis

“…8 Recent studies also show that IFN␤ has a beneficial effect on the disease course in relapsing-remitting multiple sclerosis (MS) patients, shown by reductions in both the magnetic resonance imaging lesions and the severity and frequency of relapse. 9,10 Unlike clinical trials with IFN␥ which have led to a worsening of the clinical state, the former has shown certain benefit. 9,11 As IFN␤ fails to exhibit interspecies cross-reactivity, little experimental work has been performed in experimental models and little is known about the mechanism by which this cytokine influences the disease; although, beneficial effects in the Lewis rat experimental allergic encephalomyelitis (EAE) model of MS have been found when protein IFN␤ was administered subcutaneously during the induction phase.…”

Expression of Urokinase Plasminogen Activator Receptor on Monocytes from Patients with Relapsing-Remitting Multiple Sclerosis: Effect of Glatiramer Acetate (Copolymer 1)

“…The monocyte/macrophage constitutes a large proportion of the infiltrating cells in MS lesions. Circulating monocytes from patients with MS have been shown to differ from normal monocytes in several aspects: (i) increased surface expression of interleukin-2R (52), (ii) increased oxidative burst activity (52), (iii) increased release of superoxide (15), (iv) increased phagocytic activity (31), (v) monocyte release of neopterin (17), and (vi) increased synthesis and release of a number of monokines (10,14,16,23,35,40,42), including members of the eicosanoid family (11,13,28). These results suggest that circulating monocytes from patients with MS are activated.…”