Correlation of interleukin-1β and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis

Mustafa, Mahmoud M.; LeBel, Marc; Ramilo, Octavio; Olsen, Kurt; Reisch, Joan; Beutler, Bruce; McCracken, George H.

doi:10.1016/s0022-3476(89)80067-8

Cited by 274 publications

(86 citation statements)

References 20 publications

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“…Brain IL-1 b levels in adult rats and mice after peripheral LPS exposure reach levels of 50 000 pg/g (Nguyen et al, 1998) and 5000 pg/g of tissue for IL-6 (Meyer et al, 1997). Levels in human CSF in the setting of infection range as high as 8000 pg/ml for IL-1b in CSF after aseptic meningitis (Ramilo et al, 1990) and 26 000 pg/ml of TNFa in CSF after bacterial meningitis (Mustafa et al, 1989). Local concentrations of cytokines at a neuronal level are likely to be much higher.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Infection and Risk for Schizophrenia: IL-1β, IL-6, and TNFα Inhibit Cortical Neuron Dendrite Development

Gilmore¹,

Jarskog²,

Vadlamudi³

et al. 2004

Neuropsychopharmacol

232

152

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Prenatal exposure to infection increases risk for schizophrenia, and we have hypothesized that inflammatory cytokines, generated in response to maternal infection, alter neuron development and increase risk for schizophrenia. We sought to study the effect of cytokines generated in response to infectionFinterleukin-1b (IL-1b), tumor necrosis factor-a (TNFa), and interleukin-6 (IL-6)Fon the dendritic development of cortical neurons. Primary mixed neuronal cultures were obtained from E18 rats and exposed to 0, 100, or 1000 units (U)/ml of IL-1b, TNFa, IL-6, or IL-1b þ TNFa for 44 h. MAP-2-positive neurons were randomly identified for each condition and the number of primary dendrites, nodes, and total dendrite length was determined. We found that 100 U of TNFa significantly reduced the number of nodes (27%, p ¼ 0.02) and total dendritic length (14%, p ¼ 0.04), but did not affect overall neuron survival. A measure of 100 U IL-1b þ TNFa significantly reduced the number of primary dendrites (17%, p ¼ 0.006), nodes (32%, p ¼ 0.001), and total dendritic length (30%, po0.0001), although it did not affect overall neuron survival. At 1000 U, each cytokine significantly reduced the number of primary dendrites (14-24%), nodes (28-37%), as well as total dendritic length (25-30%); neuron survival was reduced by 14-21%. These results indicate that inflammatory cytokines can significantly reduce dendrite development and complexity of developing cortical neurons, consistent with the neuropathology of schizophrenia. These findings also support the hypothesis that cytokines play a key mechanistic role in the link between prenatal exposure to infection and risk for schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Prenatal Infection and Risk for Schizophrenia: IL-1β, IL-6, and TNFα Inhibit Cortical Neuron Dendrite Development

Gilmore¹,

Jarskog²,

Vadlamudi³

et al. 2004

Neuropsychopharmacol

232

152

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“…Todos os pacientes com deficiência auditiva mostraram culturas de LCR positivas, isolando-se Escherichia coli ( 2 casos), Streptococcus B (2 casos), Listeria monocytogenes (1 caso), Streptococcus pneumoniae (1 caso), Flavobacterium meningosepticum (1 caso), Klebsiella pneumoniae (1 caso) e Proteus mirabilis (1 caso). Considerando que a perda auditiva neuro-sensorial está ligada à ação de várias substâncias liberadas a partir de componentes bacterianos, que desencadeiam e perpetuam a cascata inflamatória, entre elas a interleucina-1 beta 19 , é possível que o achado de bactéria no LCR tenha contribuído para a disacusia em nossas crianças. Em apoio a este mecanismo fisiopatológico existem estudos mostrando que o tratamento precoce com dexametasona na meningite bacteriana reduz significativamente a freqüência de surdez 12 , provavelmente devido à diminuição da produção de interleucina-1 beta 1519 , além da melhora dos níveis no LCR de glicose, proteína e lactato.…”

Section: Discussionunclassified

Meningite bacteriana neonatal: estudo prospectivo da evolução a longo prazo de 55 crianças

et al. 1996

Arq. Neuro-Psiquiatr.

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RESUMO -Foram estudadas prospectivamente 55 crianças que apresentaram meningite bacteriana no período neonatal, com o objetivo da analisar a frequência e o tipo de sequelas neurológicas. Todas as crianças nasceram a termo, sendo 38 do sexo masculino e 17 do feminino; a idade de início da doença variou de 3 a 28 dias. Os principais agentes etiológicos foram as enterobactérias. O tempo médio de seguimento foi 5 anos. A frequência de sequelas neurológicas foi 67,3%, representadas principalmente pelo atraso do desenvolvimento neuropsicomotor (58,2%), hidrocefalia (45,5%) e convulsões (34,5%). As alterações motoras graves ocorreram em 23,6% dos pacientes (tetraplegia, diplegia, hemiparesia e ataxia). As convulsões na fase aguda da doença e a cultura positiva do líquido cefalorraqueano estiveram associadas significativamente com a presença de sequelas. Na avaliação do desempenho escolar, realizada em 25 crianças, observaram-se dificuldades na aprendizagem em 48% dos casos, associadas significativamente à deficiência mental.PALAVRAS-CHAVE: recém-nascido, meningite, seguimento.Vários estudos têm mostrado que a meningite bacteriana neonatal representa causa importante de morbimortalidade infantil, apesar dos avanços nas áreas da terapêutica antimicrobiana e cuidados Neonatal bacterial meningitis: prospective study of the long term outcome of 55 childrenABSTRACT -Fifty-five infants who presented bacterial neonatal meningitis were prospectively studied to analyze the frequency and the type of sequelae. All the infants were full term newborns.There were 38 boys and 17 girls; the age of disease onset varied from 3 to 28 days. The causative organism was represented mainly by enterobacteriae. The median time of follow-up was 5 years. The frequency of neurologic sequelae was 63.7%, represented mainly by neuropsychomotor development delay (58.2%), hydrocephaly (45.5%) and convulsions (34.5%). Severe motor abnormalities ocurred in 23.6% of children (quadriplegia, diplegia, hemiparesia and ataxia). Convulsions in the acute phase of the disease and the positive cerebrospinal fluid culture were highly associated to sequelae. The school performance, obtained in 25 children, showed presence of disabilities in 48% of cases, which were significantly associated to mental retardation.

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“…In addition to its direct inflammatory effects, cachectin/TNF triggers the biosynthesis of other cytokines (e.g., IL-1, IL-6, PDGF) that mediate inflammation, and although the contribution of these secondary mediators to the systemic effects observed is unknown, this will be the subject of future investigations. Overproduction of cachectin/TNF in brain has been implicated in the pathogenesis of meningitis (56)(57)(58) and cerebral malaria (59); and anorexia invariably accompanies these infections. It is hoped that future studies of the role of cachectin/TNF-mediated brain inflammation in other intracerebral diseases (e.g., AIDS) may provide insight into the pathogenesis of associated hypophagia and weight loss.…”

Section: Discussionmentioning

confidence: 99%

Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

Tracey¹,

Morgello²,

Koplin³

et al. 1990

J. Clin. Invest.

213

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We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/ TNF (CHO-TNF) to: (a) determine the effects of cachectin/ TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/ TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/ TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. (J. Clin.

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Correlation of interleukin-1β and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis

Cited by 274 publications

References 20 publications

Prenatal Infection and Risk for Schizophrenia: IL-1β, IL-6, and TNFα Inhibit Cortical Neuron Dendrite Development

Prenatal Infection and Risk for Schizophrenia: IL-1β, IL-6, and TNFα Inhibit Cortical Neuron Dendrite Development

Meningite bacteriana neonatal: estudo prospectivo da evolução a longo prazo de 55 crianças

Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

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