Tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 in the cerebrospinal fluid of newborn with meningitis

OBJETIVO: Analisar a utilidade da dosagem dos níveis de fator de necrose tumoral-a(TNF-a), interleucin-1b(IL-1b) e interleucina-6(IL-6) no líquido cefalorraqueano (LCR) para o diagnóstico precoce e avaliação do prognóstico da meningite neonatal. MÉTODO: Foram estudados 54 recém-nascidos submetidos à punção lombar.Trinta pacientes apresentavam meningite e 24 constituíram o grupo controle. As amostras de LCR e sangue foram obtidas no momento da suspeita clínica de meningite e estocadas a - 700C.A dosagem de citocinas foi feita pelo método ELISA (enzyme-linked immunosorbent assay). RESULTADOS: Foram detectadas citocinas no LCR em todos os neonatos com meningite. O TNF-a foi detectado em 63,3% dos casos, a IL-1b em 73,3% e a IL-6 em 96,6%. Os níveis liquóricos foram significativamente mais elevados do que os séricos nos neonatos com meningite. Não houve correlação entre os níveis de citocinas no LCR e complicações neurológicas. CONCLUSÃO: A detecção de TNF-a, IL-1b e IL-6 no LCR é de grande valor para o diagnóstico precoce de meningite neonatal. Entre as três citocinas analisadas, a IL-6 foi o melhor indicador de inflamação meníngea.

Recent advances in the pathophysiology of meningitis in children

Over the past decade, much has changed on the landscape of meningitis. The purpose of this study was to investigate the involvement of nitric oxide [NO] and tumor necrosis factor alpha [TNF-alpha] in the pathogenesis of childhood meningitis. We measured the concentration of NO[-][2] [a stable metabolite of NO] and TNF-alpha in serial samples of cerebrospinal fluid [CSF] from 21 children with septic and 18 with aseptic meningitis and 20 control patients without meningitis. Significantly higher CSF NO[2] concentrations were detected in those with bacterial meningitis than those with aseptic meningitis [27.6 +/- 26.8 versus 12.2 +/- 12.3 micro mol/L; P<0.001] or among non-meningitis subjects [13.2 +/- 24.2 micro mol/L; P<0.0001]. Clinical and laboratory improvement following administration of antibiotics and dexamethasone was associated with a fall in CSF [NO[-][2] to normal levels in these patients. The mean [ +/- SD] of concentration in septic meningitis was 148.74 +/- 338.77 pg/ml. There was significantly more TNF-alpha than aseptic meningitis [6.85 +/- 17.93 pg/ml; [P<0.,001] or non-meningitis [7.67 +/- 16.07 pg/ml; P<0.001]. We did not find a correlation between CSF nitrate/nitrite levels and TNF-alpha [r = 0.046]. Our findings indicate that NO and TNF- alpha [r = 0.046]. Our findings indicate that NO and TNF- alpha [r = 0.046]. Our findings indicate that NO and TNF- alpha production are enhanced in the CSF compartment of children with septic meningitis and support the hypothesis that both markers are involved in the pathophysiology of septic meningitis

Effects of MK-801 (dizocilpine) on Brain Cell Membrane Function and Energy Metabolism in Experimental Escherichia coli Meningitis in the Newborn Piglet

We evaluated the efficacy of non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) as an adjuvant therapy in experimental neonal bacterial meningitis. Meningitis was induced by injecting 10(6) colony forming units of Escherichia coli into the cisterna magna. MK-801 3 mg/kg was given as a bolus intravenous injection, 30 min before the induction of meningitis. MK-801 did not down-modulate the inflammatory parameters, such as increased intracranial pressure, cerebrospinal fluid (CSF) leukocytosis, increased lactate and TNF-alpha levels in the CSF, and hypoglycorrhachia observed in the meningitis group. MK-801 did not significantly attenuate the elevated glutamate concentration in the CSF. However, MK-801 showed some neuroprotective effects as evidenced by significant attenuation of cerebral lipid peroxidation products (conjugated dienes) and increase of brain high-energy phosphate compounds (ATP and PCr). Improvement in cerebral cortical cell membrane Na+, K+ -ATPase activity did not reach a statistical significance. These results suggest that MK-801 was effective in ameliorating brain injury in neonatal bacterial meningitis, although it failed to attenuate the inflammatory responses.

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF) and serum levels of soluble intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in both serum and CSF samples. Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657 + or - 124.9 ng/ml) or remission (627 + or - 36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum and CSF, indicate the existence of a continuous inflammatory process within the brain tissue of MS patients despite absence of clinical signs of disease activity

Cytokine Levels in Cerebrospinal Fluid and Delayed Ischemic Deficits in Patients with Aneurysmal Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) induces an inflammatory reaction and may lead to ischemic brain damage. The pathogenesis of brain dysfunction and delayed ischemic symptoms remain difficult to understand despite extensive surveys of such reactions. Cytokine production in the central nervous system following SAH and its relation with clinical outcome have hardly been studied. This study was aimed to determine whether the levels of IL-1 beta, IL-6 and TNF-alpha in the initial cerebrospinal fluid would increase following aneurysmal SAH, and be related with development of delayed ischemic deficit and clinical outcome. Nineteen patients suffering from aneurysmal SAH and 12 control volunteers were the subjects in this study. Cerebrospinal fluid samples were obtained on admission and the levels of each cytokine were determined with enzyme-linked immunosorbent assay. Patients with aneurysmal subarachnoid hemorrhage showed elevated levels of IL-1 beta, and TNF-alpha on admission. The patients with poor neurological status showed high levels of IL-1 beta, and IL-6. The patients who developed delayed ischemic deficit had high level of IL-6. We suggest that elevated level of IL-6 in cerebrospinal fluid of patients with aneurysmal SAH on admission can predict the high risk of delayed ischemic deficit.

Interleukin-5 and interleukin-10 are major cytokines in cerebrospinal fluid from patients with active neurocysticercosis

Neurocysticercosis (NCC) is a common neurological disorder especially in developing countries, caused by infection of the brain with encysted larvae of the tapeworm Taenia solium. Seizures are a common finding associated with this disease. The objective of the present study was to evaluate the correlation between the levels of various cytokines present in the cerebrospinal fluid (CSF) of patients with NCC and the severity of the disease. The levels of the cytokines IL-1î, TNF-alpha, IL-5, IL-10 and IFN-gamma were determined in the CSF of 22 patients with active NCC, 13 patients with inactive NCC and 15 control subjects. CSF from patients with active NCC presented significantly higher IL-5 levels compared to control subjects. IL-5 and IL-10 levels in CSF from NCC patients with inflammatory CSF were significantly higher than those detected in non-inflammatory CSF. These results show a predominant Th2 lymphocyte activation in human NCC and also indicate the possible use of cytokines in the CSF as a marker for the differential diagnosis between inactive disease and the active form of NCC