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Matrix metalloproteinase-9 (MMP-9) is involved in blood–brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNβ-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNβ-1a. Twenty-one relapsing–remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNβ-1a (Rebif® 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P <0.0001), as well as the numbers of 'active' lesions ( P ranging from 0.0004 to 0.005) decreased during treatment. Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate =0.85; P <0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TIMP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF) samples from patients with neurological diseases. Patients with relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels comparable to those from patients with inflammatory neurological diseases (INDs), but higher than patients with non-inflammatory neurological diseases (NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison with inactive RR-MS implying that MMP-9 in MS is related with clinical disease activity. A correlation between the CSF/serum albumin (Q[sub Alb]) and CSF/serum MMP-9 (Q[sub MMP-9]) was observed in IND and NIND but not in RR-MS patients, indicating that CSF MMP-9 levels in NIND and IND patients could be influenced by serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients had higher values of Q[sub MMP-9]:Q[sub Alb] (MMP-9 index) than IND and NIND patients suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal synthesis of MMP-9. A significant inverse correlation was found between MMP-9 and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute to BBB disruption and T-lymphocyte entry into the CNS. [ABSTRACT FROM AUTHOR]

The validity of serum sICAM-1 levels to assess Multiple Sclerosis (MS) activity was evaluated in 49 untreated definite relapsing-remitting (RR) patients. sICAM-1 levels were significantly (P = 0.0009) higher in the ‘clinically active’ group (No 22) than in the ‘clinically inactive’ (No 27), whereas no different values were found between patients with Gd-enhancing lesions at MRI (Gd-positive) (No 32) and patients without such lesions (Gd-negative) (No 17) independently of their clinical activity. Among the ‘clinically active’ MS, the Gd-positive (No 16) subgroup showed significant (P<0.05) lower sICAM-1 levels when compared to the Gd-negative (No 6) subgroup, but higher (P = 0.009) than those of the ‘clinically inactive Gd-positive’ (No 16) patients. The sICAM-1 levels did not differ between the two ‘clinically inactive’ subgroups Gd-positive (No 16) and Gd-negative (No 11). Finally the clinically active Gd-negative (No 6) showed sICAM-1 levels higher (P = 0.002) than the clinically inactive Gd-negative (No 11). The specificity of high serum sICAM-1 levels (above M±2 s.d. of control values) to assess the disease activity in MS resulted higher (100%) using clinical than Gd-MRI activity (76%) as gold standard. The changes induced by 1 year recombinant Interferon-β-1b (rIFNβ-1b) treatment on sICAM-1 serum levels were also longitudinally investigated in 36 of the 49 RR MS. sICAM-1 levels at baseline significantly increased in the first 2 months (baseline vs 1st month P<0.0001 and 1st vs 2nd month P=0.02), persisted at high levels without any significant change after 3 months, showed a temporary decrease at 6 months, then significantly increased again at 9 and 12 months. Fourteen patients experienced relapses, with a total of 20 relapses, during the whole treatment duration. The mean relapse/rate and the frequency of patients with Gd-positive MRI scans resulted significantly higher in the first semester compared to the second semester of treatment. This study adds further insights into the validity of serum sICAM-1 to assess disease activity in MS and on the immunomodulatory properties of rIFNβ-1b. [ABSTRACT FROM AUTHOR]

Serum and cerebrospinal fluid (CSF) soluble Intercellular adhesion molecule-1 (ICAM-1) levels were evaluated (ELISA) in 22 untreated and 13 corticosteroid-treated active relapsing remitting (RR) Multiple Sclerosis (MS), in 10 untreated and 10 corticosteroid-treated Guillain-Barré syndrome (GBS) and in 17 non-inflammatory neurological diseases (NIND). Twenty-eight clinically inactive RR MS were assayed for serum sICAM-1 before and after 3 months treatment of 8 MIU rIFNβ-1b taken s.c. every other day. High sICAM-1 serum levels above the NIND values were found in untreated clinically active MS and in untreated GBS (P<0.05) but not in the untreated clinically inactive MS group. The active MS group showed significantly (P=0.0001) higher sICAM-1 serum levels if compared to the inactive group. Corticosteroid-treated active MS and GBS patients showed lower (P<0.05) serum sICAM-1 levels than the corresponding untreated groups. Serum sICAM-1 levels after 3 months of rIFNβ-1b treatment (P<0.0001, paired t-test) resulted increased compared to pretreatment values in MS. The mean values of CSF/serum sICAM-1:CSF/serum Albumin ratios (sICAM-1 Index) in active untreated MS patients were higher compared to NIND (P<0.005) and to corticosteroid-treated MS group (P=0.01). sICAM Index values in GBS did not differ from those in NIND. The results seem to suggest potential roles for serum sICAM-1 in downregulating the ongoing inflammatory response at the blood-brain barrier level and for CSF sICAM-1 in the maintenance of a central nervous system local immune response. [ABSTRACT FROM AUTHOR]