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-beta), 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-1beta, TNF-alpha), 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-1beta and TNF-alpha 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-beta, had additive effects in modulating TNF-alpha and MMP-9. These immunomodulatory responses to quercetin were similar between MS patients and healthy control (HC) subjects.
Subject(s)
Antioxidants/pharmacology , Immunologic Factors/pharmacology , Interferon-beta/pharmacology , Leukocytes, Mononuclear/drug effects , Multiple Sclerosis/immunology , Quercetin/pharmacology , Adult , Case-Control Studies , Cell Proliferation/drug effects , Cytokines/metabolism , Dose-Response Relationship, Drug , Female , Humans , Leukocytes, Mononuclear/immunology , Male , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 9/metabolism , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/pathology , Young AdultABSTRACT
Multiple sclerosis is characterized by the dual pathological processes of inflammation and neurodegeneration. Conventional MRI techniques are considered the best tools for assessing and monitoring lesion burden and inflammation but are limited in their ability to assess axonal loss. Optical coherence tomography (OCT) is a simple high-resolution technique that uses near infrared light to quantify the thickness of the retinal nerve fiber layer (RNFL), which contains only non-myelinated axons. RNFL thickness (RNFLT) was measured using OCT on thirty consecutive MS patients (60 eyes). Eighteen patients underwent quantitative MRI analysis including T1- and T2-lesion volumes (LV), normalized brain volume (NBV), normalized cortical, white and gray matter volumes (NCV, NWMV, and NGMV), and mean whole brain diffusivity (MD). There was a strong association between NBV and average RNFL thickness (p<0.001, partial rp=0.77). The T2-LV and NWMV were significantly associated with average RNFL thickness (p=0.002, partial rp= -0.76 and p=0.005, partial rp=0.68, respectively) and there were trends toward association with T1-LV (p=0.041) and NGMV (p=0.067). There was negative correlation between average RNFL thickness (average of both eyes) and disability as assessed by EDSS (p=0.02). The results support potential usefulness of OCT for MS patient monitoring and research applications.
