Abstract
INTRODUCTION. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The etiology of MS is immune. Cytokines produced by these infiltrating cells appear to be involved in the pathogenesis of inflammatory demyelination. The osteopontin (OPN) is a proimflammatory cytokine, classified as a Th1 cytokine. OPN is widely produced by a variety of immune cells including T cells, macrophages and NK cells. OPN exhibits pleiotropic functions including roles in inflammation, cell-mediated immunity and cell survival; also has recovery functions including tissue remodeling and anti-inflammatory properties inhibiting nitric oxide production in macrophages.PATIENTS AND METHOD. Two-hundred and twenty-one patients with multiple sclerosis were included in the study and 36 healthy controls. 115 relapsing-remitting MS (RRMS) patients (46 in clinical remission, 26 in relapse and 43 patients that had been receiving therapy with interferon (IFN)-beta); 35 secondary-progressive MS (SPMS) and 71 primary-progressive MS (PPMS). Disability was measured using the Kurtzke´s expanded disability status scale (EDSS). Peripheral blood was collected by standard venipuncture into vacuum tubes with EDTA. Levels of OPN in plasma samples were measured with a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) using a commercially available kit.
RESULTS AND DISCUSSION. Levels of OPN in plasma were significantly elevated in SPMS patients compared with healthy controls, RRMS patients in remission, and PPMS patients. Patients with RRMS during relapses presented significantly higher OPN plasma levels than RRMS patients in clinical remission (p=0,004). In this respect, it could be hypothesized that OPN has to play a role as a proinflammatory cytokine in acute disease activity. Levels of OPN in plasma were significantly elevated in SPMS patients with no disease progression in the last year (p=0,005). Thus suggesting a role of OPN in promoting recovery in the progression of SPMS. Not found differences between OPN levels to the primary progressive form of MS and HC. Neither found differences between OPN plasma levels of RRMS patients receiving therapy with IFN-beta and untreated RRMS patients.
CONCLUSIONS. 1) OPN has proinflammatory properties in acute disease activity; 2) OPN plays a role in promoting recovery in the progression stage of SPMS; 3) OPN is not implicated to EMPP pathogenesis; and 4) IFN beta effect is not mediated through changes in OPN production.
| Date of Award | 24 May 2004 |
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| Original language | Spanish |
| Supervisor | Xavier Montalban Gairin (Director) & Vicente Fonollosa Pla (Tutor) |