Blood Serum Cytokines in Patients with Subacute Spinal Cord Injury: A Pilot Study to Search for Biomarkers of Injury Severity

Abstract

Background. Despite considerable interest in the search for a spinal cord injury (SCI) therapy, there is a critical need to develop a panel of diagnostic biomarkers to determine injury severity. In this regard, there is a requirement for continuing research into the fundamental processes of neuroinflammatory and autoimmune reactions in SCI, identifying changes in the expression of cytokines. Methods. In this pilot study, an extended multiplex analysis of the cytokine profiles in the serum of patients at 2 weeks post-SCI (n = 28) was carried out, together with an additional assessment of neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF) levels by enzyme-linked immunosorbent assay. A total of 16 uninjured subjects were enrolled as controls. Results. The data obtained showed a large elevation of IFNγ (>52 fold), CCL27 (>13 fold), and CCL26 (>8 fold) 2 weeks after SCI. The levels of cytokines CXCL5, CCL11, CXCL11, IL10, TNFα, and MIF were different between patients with baseline American Spinal Injury Association Impairment Scale (AIS) grades of A or B, whilst IL2 (>2 fold) and MIP-3a (>6 fold) were significantly expressed in the cervical and thoracic regions. There was a trend towards increasing levels of NSE. However, the difference in NSE was lost when the patient set was segregated based on AIS group. Conclusions. Our pilot research demonstrates that serum concentrations of cytokines can be used as an affordable and rapid detection tool to accurately stratify SCI severity in patients.

Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration

“…Interestingly, the upregulation of proinflammatory cytokines TNFɑ and IL-1β persists in the serum 28 days after SCI in a rat, while IL-4 is downregulated at 28 days and there is no significant change in IL-10 at this timepoint [ 21 ]. However, Ogurcov et al [ 15 ] found a decreased concentration of both IL-1β and IL-10 in serum of human patients 14 days after SCI. Furthermore, they report the elevation of IL-4 and IFN-γ levels at this timepoint [ 15 ].…”

“…However, Ogurcov et al [ 15 ] found a decreased concentration of both IL-1β and IL-10 in serum of human patients 14 days after SCI. Furthermore, they report the elevation of IL-4 and IFN-γ levels at this timepoint [ 15 ]. In general, analysis of cytokine in CSF and serum display similar patterns as the local response in injured spinal tissue (Figs.…”

Ultrafast Doppler imaging and Ultrasound Localization Microscopy reveal the complexity of vascular rearrangement in chronic spinal lesion

“…We previously showed that UDI and ULM are applicable to human brain , both non-invasively in neonates 35 and adults 36 , and also during perioperative interventions in adult patients 37 . The precise analysis of vasculature state, along with other biomarkers previously described (blood serum cytokines, MRI, DTI [38][39][40][41] ) would provide a more complete picture of the pathophysiological changes in patients with various degrees of injury severity, and allow for a re ned/more accurate prognosis in view of the long-term follow up of these patients.…”

Peripheral white blood cell responses as emerging biomarkers for patient stratification and prognosis in acute spinal cord injury

“…The same considerations apply to nonprotein-based biomarkers such as cell-free DNA [ 40 ] and microRNAs [ 41 ]. We would add that these limitations, real or perceived, may also be time-dependent, with emerging research suggesting that cytokine measurements can be more useful during the postacute phase [ 42 ]. The risk of confounding peripheral responses can be easily mitigated, however, by focusing on nongeneric molecular biomarkers that have high CNS tissue specificity.…”