Elsevier

Brain and Development

Volume 30, Issue 2, February 2008, Pages 95-99
Brain and Development

Original article
Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis

https://doi.org/10.1016/j.braindev.2007.06.006Get rights and content

Abstract

It is known that the use of adjunctive dexamethasone in bacterial meningitis reduces audiologic and neurologic sequelae. The cerebrospinal fluid (CSF) level of soluble tumor necrosis factor 1 (sTNFR1) is an important indicator of neurologic sequelae in bacterial meningitis. We measured the CSF levels of IL-6 and sTNFR1 before administration of antibiotics (CSF1) and 1–3  days after administration of antibiotics (CSF2) in nine patients with bacterial meningitis who received dexamethasone sodium and five without dexamethasone. The CSF2 IL-6 levels of patients with/without dexamethasone were significantly lower than for CSF1 IL-6 levels (p = 0.0077, and p = 0.0431, respectively). There were no significant differences of the ratio of CSF2/CSF1 IL-6 levels between patients with dexamethasone and those without dexamethasone. CSF2 sTNFR1 levels of patients with dexamethasone were significantly lower than for CSF1 sTNFR1 levels (p = 0.0208). However, CSF2 sTNFR1 levels of patients without dexamethasone were significantly higher than for CSF1 sTNFR1 levels (p = 0.0422). The ratio of CSF2/CSF1 sTNFR1 levels of patients with dexamethasone was significantly lower than that without dexamethasone (p = 0.0063). Our present study suggests that dexamethasone inhibits increase of CSF sTNFR1 levels after antibiotics therapy in bacterial meningitis.

Introduction

Bacterial meningitis remains a serious and life-threatening disease. The use of dexamethasone sodium reduces the risk of hearing impairment in children with Haemophilus influenzae type b meningitis [1]. Previous papers have described beneficial effects of dexamethasone for bacterial meningitis [2], [3], [4], [5], [6]. In addition, previous studies have revealed that various proinflammatory cytokines play important roles in the pathogenesis of bacterial meningitis [7], [8], [9], [10]. We have demonstrated that soluble tumor necrosis factor receptor 1 (sTNFR1) is a predicting indicator of neurological sequelae in bacterial meningitis, but not interleukin-6 (IL-6) [10], [11]. Several studies have demonstrated effects of dexamethasone on CSF levels of inflammatory mediators in bacterial meningitis [12], [13]. However, there has been no report about the effects of dexamethasone on CSF sTNFR1 levels in bacterial meningitis.

To determine the effects of dexamethasone on cerebrospinal fluid (CSF) cytokines in bacterial mienigitis, we determined the CSF concentrations of IL-6 and sTNFR1 in the affected patients with/without dexamethasone therapy serially.

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Patients and methods

Informed consent was obtained from the parents of the patients and controls enrolled in this study.

Results

The CSF concentrations of IL-6 of control subjects were all below the detection limits. The CSF concentrations of sTNFR1 in control subjects were 0.9 ng/ml (median; range, 0.1–1.5 ng/ml). Serial CSF concentrations of IL-6 and sTNFR1 in patients with bacterial meningitis are shown in Fig. 1, Fig. 2. CSF1 IL-6 and sTNFR1 concentrations were significantly higher than those in controls (p < 0.0001, and p < 0.0001, respectively). CSF2 IL-6 levels of patients with/without dexamethasone were significantly

Discussion

IL-6 is a cytokine well known to play an important role in inflammatory responses. It is recognized as a primary mediator in the pathogenesis of inflammation [14], [15]. Previous studies have shown that CSF IL-6 is often elevated in patients with inflammatory disorders of the CNS, including bacterial meningitis [16], [17], [18], [19], [20]. However, CSF IL-6 levels are not related to neurological sequelae in bacterial meningitis [10]. The CSF IL-6 concentrations of 4 patients who had a relapse

Acknowledgements

This study was supported by grants from the Ministry of Health, Labor and Welfare (H18-Shinkou-6) and the Ministry of Education, Culture, Sports, Science and Technology (A-17209037), Japan.

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