Abstract
The study is aimed to determine the role of quercetin (3,3′4′,5,7-pentahydroxy flavone),
alone and in combination with human interferon-beta (IFN-β), in modulating the immune
response(s) of peripheral blood mononuclear cells (PBMC) isolated from multiple sclerosis
(MS) patients and from normal healthy subjects. PBMC proliferation in the presence
or absence of these drugs was determined and the production of proinflammatory cytokines
(IL-1β, TNF-α), and the ratio of cell migration mediator MMP-9, and its inhibitor,
TIMP-1 were assessed in the culture supernatants. Quercetin reduced, in a dose-dependent
manner, the proliferation of PBMC and modulated the level of IL-1β and TNF-α released
by PBMC in the culture supernatants. Quercetin reduced the MMP-9/TIMP-1 ratio via
lowering MMP-9 production. Quercetin, when combined with IFN-β, had additive effects
in modulating TNF-α and MMP-9. These immunomodulatory responses to quercetin were
similar between MS patients and healthy control (HC) subjects.
Keywords
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References
- Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment.Mult. Scler. 2005; 11: 441-446
- Pharmacokinetics and modeling of quercetin and metabolites.Pharmaceutical Research. 2005; 22: 892-901
- Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia.Neurosci. Lett. 2006; 404: 330-335
- Interferon-beta1a for the treatment of multiple sclerosis.[Review] Expert Opin. Biol. Ther. 2007; 7: 535-542
- Interferon-beta not only inhibits interleukin-1beta and tumor necrosis factor-alpha but stimulates interleukin-1 receptor antagonist production in human peripheral blood mononuclear cells.[Review] Eur. Cytokine Netw. 1997; 8: 345-349
- Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects.J. Nutr. 1998; 128: 593-597
- Cell culture protection and in vivo neuroprotective capacity of flavonoids.Neurotox. Res. 2003; 5: 425-432
- Analgesic, antiinflammatory and CNS depressant activities of sesquiterpenes and a flavonoid glycoside from Polygonum viscosum.Pharmazie. 2004; 59: 222-225
- Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis.[Review] Neurology. 2002; 58: S3-S9
- Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis.[Review] Neurology. 2007; 68 (discussion S43–54): S13-S21
- Toxicity and carcinogenicity studies of quercetin, a natural component of foods.Fundam. Appl. Toxicol. 1992; 19: 423-431
- Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis.Mult. Scler. 2006; 12: 294-301
- PRISMS Study Group. Interferon beta-1a in MS: results following development of neutralizing antibodies in PRISMS.Neurology. 2005; 65: 48-55
- Inhibitory effect of sofalcone on tumor necrosis factor-alpha and interleukin-1 beta production in human monocytes stimulated by Helicobacter pylori water extract.Drugs Exp. Clin. Res. 2001; 27: 103-106
- Absorption of three wine-related polyphenols in three different matrices by healthy subjects.Clin. Biochem. 2003; 36: 79-87
- Flavonoids influence monocytic GTPase activity and are protective in experimental allergic encephalitis.J. Exp. Med. 2004; 200: 1667-1672
- Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450.[Review] Chem.-Biol. Interact. 2002; 139: 1-21
- Immunological update on multiple sclerosis.[Review] Curr. Opin. Neurol. 2001; 14: 299-304
- Bioavailability of the dietary antioxidant flavonol quercetin in man.Cancer Lett. 1997; 114: 139-140
- Oral administration of catechin protects against ischemia–reperfusion-induced neuronal death in the gerbil.Free Radic. Res. 1998; 29: 359-365
- Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation.J. Neurosci. 1999; 19: 8114-8121
- European Interferon Beta-1a IM Dose-Comparison Study Investigators. Neutralizing antibodies and efficacy of interferon beta-1a: a 4-year controlled study.Neurology. 2005; 65: 40-47
- Treatment of interstitial cystitis with a quercetin supplement.Tech. Urol. 2001; 7: 44-46
- Disposition of the flavonoid quercetin in rats after single intravenous and oral doses.Drug Dev. Ind. Pharm. 2003; 29: 397-403
- Baseline T cell reactivity in multiple sclerosis is correlated to efficacy of interferon-beta.J. Neuroimmunol. 2002; 133: 217-224
- Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha.Curr. Pharm. Des. 2006; 12: 4271-4279
- Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression.Biochem. Pharmacol. 2005; 69: 395-406
- Ribavirin and quercetin synergistically downregulate signal transduction and are cytotoxic in human ovarian carcinoma cells.Oncol. Res. 1999; 11: 243-247
- The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis.Brain. 2001; 124: 1743-1753
- Physiopathologic relationship between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases].[Review] Arch. Esp. Urol. 2004; 57: 25-34
- Recommended diagnostic criteria for multiple sclerosis, guidelines from the International Panel on the diagnosis of multiple sclerosis.Ann. Neurol. 2001; 50: 121-127
- Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1/2, cell-cycle regulation, and matrix metalloproteinase-9.Biochem. Biophys. Res. Commun. 2003; 301: 1069-1078
- Inhibitory effect of quercetin on carrageenan-induced inflammation in rats.Life Sci. 2003; 74: 709-721
- Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte.J. Clin. Immunol. 2004; 24: 542-552
- The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-kappa beta system.Clin. Vaccine Immunol.: CVI. 2006; 13: 319-328
- Statins as immunomodulators: comparison with interferon-beta 1b in MS.Neurology. 2002; 59: 990-997
- T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases.Brain. 2001; 124: 2203-2214
- Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease.J. Neurochem. 2003; 87: 172-181
- Determination of St. John's wort flavonoid-metabolites in rat brain through high performance liquid chromatography coupled with fluorescence detection.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2006; 832: 109-113
- Interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor type I and II, and soluble E-selectin serum levels in multiple sclerosis patients receiving weekly intramuscular injections of interferon-beta1a.Eur. Cytokine Netw. 2000; 11: 81-86
- Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis.Mult. Scler. 2005; 11: 169-174
- Alternative and accessory pathways in the regulation of IFN-beta-mediated gene expression.[Review] J. Interferon Cytokine Res. 2005; 25: 788-798
- Monocyte activation in multiple sclerosis.Mult. Scler. 1998; 4: 162-168
- Matrix metalloproteinases and neuroinflammation in multiple sclerosis.[Review] Neuroscientist. 2002; 8: 586-595
- Effects of combination therapy of beta-interferon 1a and prednisone on serum immunologic markers in patients with multiple sclerosis.Mult. Scler. 2003; 9: 28-31
- Chemokines and matrix metalloproteinase-9 in leukocyte recruitment to the central nervous system.[Review] Brain Res. Bull. 2003; 61: 347-355
- Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection.Brain Res. Bull. 2007; 73: 55-63
- Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion.Biochem. Pharmacol. 1999; 57: 199-208
- Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability.J. Biol. Chem. 2003; 278: 34783-34793
- Synergistic action of quercetin and murine alpha/beta interferon in the treatment of Mengo virus infection in mice.Antivir. Res. 1987; 7: 169-178
- The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells.Biochem. Pharmacol. 2004; 68: 621-629
- Flavonoids: antioxidants or signalling molecules?.[Review] Free Radic. Biol. Med. 2004; 36: 838-849
- Multiple sclerosis disease-modifying therapies: adverse effect surveillance and management.[Review] Expert Rev. Neurother. 2006; 6: 333-346
- Cytokine mRNA expression in inflammatory multiple sclerosis lesions: detection by non-radioactive in situ hybridization.Cytokine. 1993; 5: 583-588
- Flavonoid permeability across an in situ model of the blood-brain barrier.Free Radic. Biol. Med. 2004; 36: 592-604
Article info
Publication history
Published online: October 16, 2008
Accepted:
September 5,
2008
Received in revised form:
August 27,
2008
Received:
April 28,
2008
Identification
Copyright
Published by Elsevier Inc.