Increased levels of cytokines in cerebrospinal fluid of children with aseptic meningitis caused by mumps virus and echovirus 30.

We measured levels of pro-inflammatory cytokines in the cerebrospinal fluid (CSF) of patients with mumps meningitis, enteroviral echovirus 30 meningitis and children without central nervous system infection to investigate whether these molecules were involved in the pathogenesis of viral meningitis. The CSF was obtained from 62 children suspected with meningitis. These patients were classified to the mumps meningitis (n = 19), echovirus 30 meningitis (n = 22) and non-meningitis (n = 21) groups. The concentrations of interleukin-1 (IL-1), interleukin-1 soluble receptor type 2 (IL-1R2), interleukin-8 (IL-8), human interferon gamma (IFN-γ) and human tumour necrosis factor alpha (TNF-α) were determined by immunoassay. A significant increase was noted in the levels of IL-8, TNF-α and IL-1R2 in the CSF of both meningitis groups as compared to controls. The concentrations of IFN-γ and IL-1 differed significantly only between the mumps group and control. The levels of IL-1, IFN-γ and TNF-α were significantly higher in mumps meningitis when compared to the echovirus 30 group. Of all cytokines examined, only IFN-γ correlated with pleocytosis (r = 0.58) in the mumps meningitis group. The increased CSF cytokine levels are markers of meningeal inflammation, and each virus may cause a specific profile of the cytokine pattern.

Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease.

PURPOSE: Obesity, insulin resistance and dyslipidemia are the most significant risk factors of non-alcoholic fatty liver disease (NAFLD) but the role of adipokines in patomechanism of this disease is not clear. The aim of the study was to evaluate the serum levels of leptin, adiponectin and resistin in obese children with NAFLD. MATERIAL/METHODS: The fasting serum levels of adipokines were determined in 44 consecutive obese children with suspected liver disease and in 24 lean controls. The degree of the ultrasound liver steatosis was graded according to Saverymuttu. RESULTS: The fatty liver was confirmed in 33 children by ultrasonography (16 of them also showed an increased ALT activity). The serum leptin level was significantly higher and adiponectin level was lower in the obese children with NAFLD when compared to controls. Only adiponectin correlated with homeostasis model assessment of insulin resistance (HOMA-IR). Significant negative correlations were found between the ultrasonographic grades of liver steatosis and adiponectin and resistin levels. Serum adiponectin and resistin levels were lower in children with an advanced liver steatosis (grade 3, n=10) compared to patients with a mild steatosis (grade 1-2, n=23). The ability of serum adiponectin and resistin to differentiate children with an advanced liver steatosis from those with mild steatosis was significant. CONCLUSIONS: These data suggest a role of both adiponectin and resistin in the pathogenesis of NAFLD in obese children and confirm the association between adiponectin and insulin resistance. Adiponectin and resistin may be suitable serum markers in predicting an advanced liver steatosis in children with NAFLD.

Elevated levels of MMP-9 and TIMP-1 in the cerebrospinal fluid of children with echovirus type 30 and mumps meningitis.

Matrix metalloproteinases are involved in leucocyte invasion into the central nervous system (CNS) during meningitis. The aim of the study was to determine whether there are differences in the expression patterns of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) in the cerebrospinal fluid (CSF) of patients with meningitis caused by one of two known distinct viral agents. Concentrations were measured by using an enzyme-linked immunosorbent assay (ELISA) in 16 children with mumps meningitis, in 25 children with echovirus type 30 meningitis and in a control group of 23 children without any CNS infection. Increased levels of MMP-9 were found in children with mumps (median 0.48 ng/ml; P < 0.001) and enteroviral meningitis (median 2.76 ng/ml; P < 0.001) compared with that in controls (median: 0.01 ng/ml). Concentrations of TIMP-1 greatly exceeded concentrations of MMP-9 and were elevated in children with mumps (median: 56 ng/ml) and echovirus type 30 meningitis (median: 55 ng/ml) compared to controls (median: 17 ng/ml). No significant differences in MMP-9 or TIMP-1 levels were detected between the two meningitis groups. The MMP-9/TIMP-1 ratio was greater in children with echovirus type 30 than in those with mumps meningitis. There was no correlation between MMP-9 levels and total CSF cell count. MMP-9 correlated with CSF absolute neutrophil count in children with echovirus type 30 meningitis (r = 0.431; P < 0.05). The concentration of MMP-9 is higher in children with viral meningitis, possibly because of infiltrating polymorphonuclear cells present in the initial phase of the disease.

Increase in adhesion molecules in cerebrospinal fluid of children with mumps and mumps meningitis.

Adhesion molecules play a key role in leucocyte migration into the central nervous system (CNS). Concentrations of endothelial-derived soluble intercellular adhesion molecule-1 (sICAM-1) and leucocyte-originated soluble L-selectin (sL-selectin) in cerebrospinal fluid (CSF) of children with mumps meningitis (mononuclear pleocytosis, n = 33) and mumps (absence of pleocytosis, n = 9) were compared with values from age-matched control group (n = 19). In 14 patients from the meningitis group, adhesion molecule levels together with albumin concentration were estimated in paired CSF/serum samples to calculate concentration quotients and determine molecule intrathecal release. Both sICAM-1 (median 3.44 versus 0.86 ng/ml; P < 0.0001) and sL-selectin (median 29.91 versus 8.52 ng/ml; P < 0.0001) concentrations in CSF were increased in mumps meningitis patients compared with controls. Increased levels of the selected adhesion molecules were also observed in mumps patients without CNS involvement when compared with controls (median sICAM-1: 1.14 versus 0.86 ng/ml, sL-selectin: 13.54 versus 8.52 ng/ml; P < 0.01). Additionally, the concentration of adhesion molecules was found to correlate with CSF leucocyte count. Considerable correlation of sICAM-1 and sL-selectin quotients and corresponding albumin quotients suggests that a majority of the soluble adhesion molecules originated from the bloodstream. Analysis of adhesion molecule levels demonstrated indirect evidence of brain-derived fractions. Our results suggest the involvement of adhesion molecules during the early phase of mumps meningitis.