The role of matrix metalloproteinases and tumor necrosis factor alpha in the multiple sclerosis disease

PURPOSE: In this study on definite MS diagnosed patients, we have aimed to find out the relationship between matrix metalloproteinases (MMP-9, MMP-2), specific inhibitors (TIMP-1, TIMP-2) and tumor necrosis factor alpha (TNF ) and its role in MS disease.MATERIAL AND METHOD: This study includes 41 females and 19 males, in total 60 MS patient, 18-60 aged who are cured with immunmodulatuar for at least 1 year in Dicle University neurologic clinic and have the last attacks before more than 1 month, and 19 females and 11 males, in total 30 control group adequate with age and sex. MMP-2, 9 and TIMP-1,2 were determined by ELISA (Enzyme-linked immunosorbent assay) method and TNF-alpha plasma levels were determined by Chemiluminescent (Immulite) method. Patient?s ages, sex, disease period, MS clinic subtype, start symptoms were recorded. EDSS was measured by the help of Kurtzke Expanded Disability Status Scale.RESULTS: The sex differences between groups were analysed by Q Square. The differences were found insignificand (P>0,05). The age distribution between groups was analysed by Anova test. The differences between groups were found significand. However, when the groups were compared in pair using Post Hoc, Bonfrroni correction, the differences were not significand between groups (P>0,05).The laboratuary values (MMP-2, 9; TIMP-1,2 ve TNF-?), were analysed by Anova test according to five groups( ? 5 year RRMS, ? 10 year RRMS, PPMS, SPMS and control ). There was only statistical significance with TNF alpha and TIMP-1. To compare ? 5 year RRMS, ? 10 year RRMS, PPMS, SPMS and control groups in pair, Post Hoc, Bonferroni correction was applied. When comparation ? 5 year RRMS and PPMS with control group, TNF-? plasma level was found statistically significant (P<0,05). When comparing PPMS group with control group, TIMP-1 plasma level was found statistically significant between these groups (P<0,05)CONCLUSIONS:The sex differences between groups were analysed by Q Square. The differences were found insignificand (P>0,05). The age distribution between groups was analysed by Anova test. The differences between groups were found significand. However, when the groups were compared in pair using Post Hoc, Bonfrroni correction, the differences were not significand between groups (P>0,05).The laboratuary values (MMP-2, 9; TIMP-1,2 ve TNF-?), were analysed by Anova test according to five groups( ? 5 year RRMS, ? 10 year RRMS, PPMS, SPMS and control ). There was only statistical significance with TNF alpha and TIMP-1. To compare ? 5 year RRMS, ? 10 year RRMS, PPMS, SPMS and control groups in pair, Post Hoc, Bonferroni correction was applied. When comparation ? 5 year RRMS and PPMS with control group, TNF-? plasma level was found statistically significant (P<0,05). When comparing PPMS group with control group, TIMP-1 plasma level was found statistically significant between these groups (P<0,05)COMMENT: In the present study, TNF alpha plasma level was statistically significant when ? 5 years RRMS and PPMS were compared to control group. TNF? plasma level in ? 5 years RRMS and PPMS groups was lower than control group.The present study shows that TNF? plasma level alone was lower in MS disease at stable period under immunmodulatuar and that it plays more active role in pathogenesis at early stages of disease and thus it can be used alone as prognose factor.TIMP-1 plasma level of PPMS group was found lower compared to control group. Since TIMP-1 is potent inhibitor of MMP-9, the increase of disability of PPMS disease may be due to low levels of TIMP-1. This indicates that the determination of TIMP-1 plasma level can be used as prognostic factor.In the literature, the significant differences in MMP-2 levels were not obtained in RRMS and SPMS patients. The present study has also found the same results. However, MMP-2 plasma levels were clearly higher in all groups with MS disease compared to control group. This indicates that the increase in MMP-2 plasma levels is effective in the stability of MS.The results obtained in the present study show that the study will shed light on pathogenesis of MS and will help to develop new treatment approach, though stil there should be more comphrensive research on the subject.KEY WORDS: Multiple sclerosis, matrix metalloproteinasses, tumor necrosis factor alpha