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Multicenter Study
. 2023 Sep:169:156310.
doi: 10.1016/j.cyto.2023.156310. Epub 2023 Jul 29.

Lower levels of Th1 and Th2 cytokines in cerebrospinal fluid (CSF) at the time of initial CSF shunt placement in children are associated with subsequent shunt revision surgeries

Tamara D Simon  1 , Sabrina Sedano  2 , Yael Rosenberg-Hasson  3 , Ramon Durazo-Arvizu  4 , Kathryn B Whitlock  5 , Paul Hodor  6 , Jason S Hauptman  7 , David D Limbrick  8 , Patrick McDonald  9 , Jeffrey G Ojemann  7 , Holden T Maecker  3 ; Cerebrospinal FLuId MicroBiota in Shunts CLIMB Study Group
Affiliations
Multicenter Study

Lower levels of Th1 and Th2 cytokines in cerebrospinal fluid (CSF) at the time of initial CSF shunt placement in children are associated with subsequent shunt revision surgeries

Tamara D Simon et al. Cytokine. 2023 Sep.

Abstract

Objective: We compare cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. We also describe the cytokine profiles across surgical episodes for children who undergo multiple subsequent revision surgeries.

Methods: This pilot study was nested within an ongoing prospective multicenter study collecting CSF samples and clinical data at the time of CSF shunt surgeries since August 2014. We selected cases where CSF was available for children who underwent an initial CSF shunt placement and had no subsequent shunt revision surgeries during >=24 months of follow-up (n = 7); as well as children who underwent an initial CSF shunt placement and then required repeated CSF shunt revision surgeries (n = 3). Levels of 92 human cytokines were measured using the Olink immunoassay and 41 human cytokines were measured using Luminex based bead array on CSF obtained at the time of each child's initial CSF shunt placement and were displayed in heat maps.

Results: Qualitatively similar profiles for the majority of cytokines were observed among the patients in each group in both Olink and Luminex assays. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Pro- and anti-inflammatory cytokines were selected a priori and shown across subsequent revision surgeries for the 3 patients. Cytokine patterns differed between patients, but within a given patient pro-inflammatory and anti-inflammatory cytokines acted in a parallel fashion, with the exception of IL-4.

Conclusions: Heat maps of cytokine levels at the time of initial CSF shunt placement for each child undergoing only a single initial CSF shunt placement and for each child undergoing repeat CSF shunt revision surgeries demonstrated qualitatively similar profiles for the majority of cytokines. Lower levels of MCP-3, CASP-8, CD5, CXCL9, CXCL11, eotaxin, IFN-γ, IL-13, IP-10, and OSM at the time of initial surgery were noted in the children who went on to require multiple surgeries. Better stratification by patient age, etiology, and mechanism of failure is needed to develop a deeper understanding of the mechanism of inflammation in the development of hydrocephalus and response to shunting in children.

Keywords: Cerebrospinal fluid; Cytokine; Hydrocephalus; Shunt placement.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tamara Simon reports financial support was provided by National Institutes of Health. Tamara Simon reports financial support was provided by National Center for Advancing Translational Sciences. David D. Limbrick reports a relationship with Mircobot Medical Inc. that includes: funding grants. No other conflict of interest to disclose.

Figures

Figure 1.
Figure 1.
Olink heatmap results showing the cytokine profiles at the time of initial surgery for children who undergo placement of an initial CSF shunt and require no revisions, vs. those requiring repeat revisions. Patients are listed along the x-axis, cytokines are listed on the y-axis, and p values generated from permutation tests are displayed next to the cytokines on the right side. Relative intensity of cytokine expression (NPX) is denoted by color gradient shown in legend to the right of the figure.
Figure 2.
Figure 2.
Dot scatterplots showing the relative intensity of cytokine expression (NPX) (y-axis) for cytokines with differences (p<0.10) noted between the time of initial surgery for patients who undergo single versus repeated surgeries (x-axis). Horizontal bars represent medians.
Figure 3.
Figure 3.
Olink heatmap results showing the cytokine profiles of patients who undergo placement of an initial CSF shunt and require repeat revision surgeries. Procedures within each patient are listed along the x-axis, and cytokines are listed on the y-axis. Relative intensity of cytokine expression (NPX) is denoted by color gradient shown in legend to the right of the figure.
Figure 4:
Figure 4:
Spaghetti plot of pro-inflammatory cytokines such as interleukin (IL) −6 and TNF-α; and anti-inflammatory cytokines such as IL-1 receptor antagonist, IL-4, IL-10, and IL-13 for patients who undergo placement of an initial CSF shunt and require repeat revisions surgeries.
See this image and copyright information in PMC

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