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

Abstract

-Objective: To analyze the usefulness of determining the cerebrospinal fluid(CSF) levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β) and interleukin-6(IL-6)for the early diagnosis and evaluation of the prognosis of neonatal meningitis. Method: We studied 54 newborn that underwent lumbar puncture.Thirty patients had meningitis and 24 were the control group.CSF and sera were obtained at the moment of suspicion of meningitis and stored at -70 0 C.Cytokines were performed by enzyme-linked immunosorbent assay method. Results: CSF cytokines were detected in all the newborn with meningitis.TNF-α was detected in the CSF in 63.3% of the neonates, IL-1β in 73.3% and IL-6 in 96.6%.The CSF levels were significantly higher than serum in neonates with meningitis.There was no correlation between the CSF levels of cytokines and neurologic complications. Conclusion: The detection of TNF-α, IL-1β and IL-6 in the CSF is of great value in order to achieve a early diagnosis of neonatal meningitis.Among the three cytokines analyzed, IL-6 was the best indicator of meningeal inflammation.KEY WORDS: meningitis, cerebrospinal fluid, newborn, tumor necrosis factor-α, interleukin-1β, interleukin-6.Fator de necrose tumoral-α a, interleucina-1β b e interleucina-6 no líquido cefalorraqueano de recém-nascidos com meningite RESUMO -Objetivo: Analisar a utilidade da dosagem dos níveis de fator de necrose tumoral-α(TNF-α), interleucin-1β(IL-1β) 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 -70 0 C.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-α foi detectado em 63,3% dos casos, a IL-1β 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-α, IL-1β 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. PALAVRAS-CHAVE: meningite, líquido cefalorraqueano, recém-nascido, fator de necrose tumoral-α, interleucin-1β, interleucina-6.

Clinical outcome of neonatal bacterial meningitis according to birth weight

“…Fifty per cent of the deaths occurred in neonates with a positive culture for enterobacteria, which is supported by other studies that show a variation in mortality according to the type of microorganism isolated from the CSF, with enterobacteria being the most virulent 15,16 . Krebs et al 8 observed signifi cantly higher levels of IL-6 in the CSF of neonates with meningitis due to gram-negative bacteria, suggesting a higher intensity of the infl ammatory process in these newborns. The brain abscess, reported in literature in 1% of meningitis cases caused by gram-negative bacteria 17 , was observed in 3,4% of our patients.…”

“…The most frequent clinical fi ndings were non-specifi c, confi rming the diffi culty of attaining an early diagnosis of neonatal meningitis, due to the absence Neonatal bacterial meningitis: outcome Krebs & Costa of neurological signs in the acute phase of the infectious process 8,9 . Fever, irritability, seizures and a bulging fontanel were signifi cantly more frequent among newborns whose birth weight was ≥2500g, whereas abdominal distension, apnea, jaundice and blood count abnormalities were predominant among low birth weight newborns.…”

Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in infants

“…This pro-inflammatory response is counter-balanced by the generation of anti-inflammatory (IL-10) and immune-modulating cytokines (IL-12) [15][16][17][18] . Elevations of pro-inflammatory cytokines are sensitive markers of bacterial meningitis and may be useful in differentiating bacterial from viral disease 13,14,[18][19][20][21][22] . However, pro-inflammatory cytokines such as TNF-α and IL-1 remain elevated only transiently, thus limiting their diagnostic utility if the LP is performed later in the course of illness, as is often the case in neonates.…”

“…While anti-inflammatory cytokines (IL-10) have been shown to be elevated in sepsis, they have been evaluated to a limited extent for their utility in the diagnosis of meningitis 17, 23 . Few studies have evaluated these markers in combination in the setting of meningitis in infants 19,22 .…”

"Sepse de origem hospitalar por Klebsiella spp. em unidades neonatais: evolução clínica"

“…Em nosso meio esta bactéria é relatada em cerca de 12,5% dos neonatos com meningite bacteriana (Krebs et al, 2005). Basu et al (2001), na Índia, descreveram um recém-nascido com abscesso cerebral, como complicação de sepse por Klebsiella pneumoniae, com suspeita de transmissão vertical, pelo fato da mãe ter apresentado infecção urinária assintomática no período antenatal.…”