Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection

Stephen J Hopkins, Catherine J McMahon, Navneet Singh, James Galea, Margaret Hoadley, Sylvia Scarth, Hiren Patel, Andy Vail, Sharon Hulme, Nancy J Rothwell, Andrew T King, Pippa J Tyrrell, Stephen J Hopkins, Catherine J McMahon, Navneet Singh, James Galea, Margaret Hoadley, Sylvia Scarth, Hiren Patel, Andy Vail, Sharon Hulme, Nancy J Rothwell, Andrew T King, Pippa J Tyrrell

Abstract

Background: Cytokines and cytokine receptor concentrations increase in plasma and cerebrospinal fluid (CSF) of patients following subarachnoid haemorrhage (SAH). The relationship between plasma and CSF cytokines, and factors affecting this, are not clear.

Methods: To help define the relationship, paired plasma and cerebrospinal fluid (CSF) samples were collected from patients subject to ventriculostomy. Concentrations of key inflammatory cytokines, interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor 2, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and TNF receptors (TNF-R) 1 and 2 were determined by immunoassay of CSF and plasma from 21 patients, where samples were available at three or more time points.

Results: Plasma concentrations of IL-1ß, IL-1Ra, IL-10, TNF-α and TNF-R1 were similar to those in CSF. Plasma TNF-R2 and IL-1R2 concentrations were higher than in CSF. Concentrations of IL-8 and IL-6 in CSF were approximately10 to 1,000-fold higher than in plasma. There was a weak correlation between CSF and plasma IL-8 concentrations (r = 0.26), but no correlation for IL-6. Differences between the central and peripheral pattern of IL-6 were associated with episodes of ventriculostomy-related infection (VRI). A VRI was associated with CSF IL-6 >10,000 pg/mL (P = 0.0002), although peripheral infection was not significantly associated with plasma IL-6.

Conclusions: These data suggest that plasma cytokine concentrations cannot be used to identify relative changes in the CSF, but that measurement of CSF IL-6 could provide a useful marker of VRI.

Figures

Figure 1
Figure 1
The median (IQR) values for cytokines and cytokine receptors in paired plasma and CSF samples from 21 patients. All time points were not available for all patients but are as identified in Figures 3 and 4 .
Figure 2
Figure 2
The median (IQR) values for IL-6 and IL-8 in paired plasma and CSF samples from 21 patients. All time points were not available for all patients but are as identified in Figures 3 and 4 .
Figure 3
Figure 3
Paired plasma and CSF samples from 21 patients were analysed for IL-8 at the times indicated.
Figure 4
Figure 4
Paired plasma and CSF samples from 21 patients were analysed for IL-6 at the times indicated.

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