TNF-á, IL-2, -6, -10, -12, -17, -23, MMP-7, MMP-9, TIMP-1 and neopterin levels in childhood multiple sclerosis patients and alterations in patients treated with interferon beta

Childhood MS is a relatively rare occurrence and because of similar clinical features with many hereditary and inflammatory diseases, diagnosis and monitoring of the disease is considerably difficult. The most important reason for this difficulty is the lack of markers indicating disease activity.We investigated in childhood RRMS patients, the levels of some cytokines which are thought to play a role in the pathogenesis of MS, matrix metalloproteinases (MMP-7 and-9) and MMP tissue inhibitors TIMP-1 which are known to play a role in the breakdown of the blood brain barrier and brain tissue and neopterin. We reevaluated these levels and observed the changes after one year in patients both treated with interferon beta and received no treatment.For this purpouse, 14 children with diagnosis of RRMS before 18 years old were included in our study. Baseline serum, CSF and urine samples were collected before treatment started. Interferon beta treatment (Avonex, Rebif, Betaferon) was started in 8 patients. A year later, serum and urine samples were taken again from all patients. Along with the samples of healthy controls at the same age and sex, the IL-2, -6, -10, -12, -17.23, MMP-7, MMP-9, TIMP-1 and neopterin were calculated in all samples by ELISA in our immunulogy laboratory.Results: None of the interleukine levels were significantly different compared to healthy controls and these levels were often below the quantifiable amount. Similarly, neopterin in urine and serum did not differ significantly in MS patients compared with healthy controls. But serum neopterin levels increased significantly in patients treated with IFN-â. MMP-9 levels were significantly higher in RRMS patients compared to healthy controls. These levels decreased significantly in patients receiving interferon beta treatment. TIMP-1 levels were significantly lower in the patient group and this level was significantly increased after one year of treatment. MMP-9/TIMP-1 ratio were significantly higher in children with RRMS and this rate also significantly decreased after treatment. MMP-7 levels were significantly lower than the control group in patients with RRMS. Serum MMP-7 significantly increased in patients treated with IFN-â but not in patients without any treatment.Conclusion: In childhood MS patients, serum and CSF MMP-7, MMP-9 levels and MMP-9/TIMP-1 ratio was significantly different than healthy controls. These differences significantly improves with the treatment of interferon beta. These markers can be used to assess the disease activity and along with serum neopterin levels, to predict response to treatment in children diagnosed with MS. There is no significant differences in interleukin or neopterin levels in pediatric RRMS patients compared with healthy controls.Key words: Childhood multiple sclerosis, interleukin, neopterin, matrix metalloproteinases, interferon beta