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Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement.

Trysberg E, Blennow K, Zachrisson O, Tarkowski A - Arthritis Res. Ther. (2004)

Bottom Line: Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay.Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012).In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden. Estelle@immuno.gu.se

ABSTRACT
Symptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.

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Related in: MedlinePlus

Cerebrospinal fluid expression of active matrix metalloproteinase (MMP)-2 in patients with systemic lupus erythematosus with (NPSLE) and without (No NPSLE) central nervous system involvement, and in cerebrally healthy control individuals.
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Figure 2: Cerebrospinal fluid expression of active matrix metalloproteinase (MMP)-2 in patients with systemic lupus erythematosus with (NPSLE) and without (No NPSLE) central nervous system involvement, and in cerebrally healthy control individuals.

Mentions: There were no statistically significant differences in CSF MMP-2 levels between NPSLE and patients without CNS lupus (499 ± 70 versus 555 ± 70 pg/ml; not significant) or compared with cerebrally healthy control individuals (499 ± 70 versus 384 ± 33 pg/ml; not significant; Fig. 2).


Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement.

Trysberg E, Blennow K, Zachrisson O, Tarkowski A - Arthritis Res. Ther. (2004)

Cerebrospinal fluid expression of active matrix metalloproteinase (MMP)-2 in patients with systemic lupus erythematosus with (NPSLE) and without (No NPSLE) central nervous system involvement, and in cerebrally healthy control individuals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064867&req=5

Figure 2: Cerebrospinal fluid expression of active matrix metalloproteinase (MMP)-2 in patients with systemic lupus erythematosus with (NPSLE) and without (No NPSLE) central nervous system involvement, and in cerebrally healthy control individuals.
Mentions: There were no statistically significant differences in CSF MMP-2 levels between NPSLE and patients without CNS lupus (499 ± 70 versus 555 ± 70 pg/ml; not significant) or compared with cerebrally healthy control individuals (499 ± 70 versus 384 ± 33 pg/ml; not significant; Fig. 2).

Bottom Line: Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay.Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012).In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology and Inflammation Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden. Estelle@immuno.gu.se

ABSTRACT
Symptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.

Show MeSH
Related in: MedlinePlus