Abstract
Background Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes. Methods Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996–2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays. Results MPO correlated positively with MMP-8 (rho 0.496, P < 0.001) and MMP-9 (rho 0.153, P = 0.02) but negatively with TIMP-1 (rho -0.361, P < 0.001). MMP-8 emerged as the best predictor of disease outcomes: a CSF MMP-8 concentration above the median increased the odds of death 4.9-fold (95% confidence interval 1.8–12.9). Conclusions CSF MMP-8 presented as an attractive prognostic marker in children with bacterial meningitis.
Highlights
Bacterial meningitis (BM) remains a significant cause of childhood mortality and morbidity globally, often affecting children in developing, resource-poor countries [1]
By measuring the Matrix metalloproteinases (MMPs)-8, MMP-9, tissue inhibitor of metalloproteinase- (TIMP-)1, and MPO levels in the cerebrospinal fluid (CSF) of children with BM, we addressed two questions in this study: First, how would these inflammatory mediators relate to each other in human subjects? Second, to what extent would the results reflect the outcomes of this severe disease?
This series comprised 245 children with bacterial meningitis originating from the Dominican Republic (n = 104), Venezuela (n = 54), Paraguay (n = 51), and Ecuador (n = 36)
Summary
Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes. Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996– 2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays. MMP-8 emerged as the best predictor of disease outcomes: a CSF MMP-8 concentration above the median increased the odds of death 4.9-fold (95% confidence interval 1.8–12.9). CSF MMP-8 presented as an attractive prognostic marker in children with bacterial meningitis
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