Cerebrospinal Fluid Interleukin-6 Levels Research Articles

Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system

The widespread use of plastics has led to increased micro- and nanoplastics (MNPs) pollution, resulting in significant environmental challenges and concerns about potential harm to human health. This study investigated whether certain types of MNPs can accumulate in the human central nervous system (CNS) and trigger inflammatory responses, particularly after CNS infection. Our analysis of 28 cerebrospinal fluid (CSF) samples from 28 patients with or without CNS infection revealed that only polystyrene (PS), polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC) were capable of selectively entering the human CNS. Concentrations of PP and PE were positively correlated with the CSF albumin index. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly increased in patients with CNS infections. However, concentrations of MNPs were not significantly associated with CSF levels of IL-6 or IL-8. Overall, these findings suggest that specific MNPs can penetrate the human CNS, especially after impairment of the blood-brain barrier. Notably, MNPs derived from commonly used plastics did not significantly induce or exacerbate inflammation in the human CNS.

Possible association of elevated CSF IL-6 levels with anxiety and frustration in psychiatric disorders.

Neuroinflammation is an important causal factor for a variety of psychiatric disorders. We previously reported increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and major depressive disorder. The present study aimed to examine the possible association of interleukin-6 levels with anxiety and frustration, negative valence symptoms shared in various psychiatric disorders. We included 129 patients with psychiatric disorders and 70 controls. CSF and plasma interleukin-6 levels were measured by immunoassay kits, and psychological symptoms were assessed with the State-Trait Anxiety Inventory, and the Basic Psychological Need Satisfaction and Frustration Scale. To examine regional cerebral blood flow, patients underwent arterial spin labeling analysis using magnetic resonance imaging. Cerebrospinal fluid interleukin-6 levels were significantly correlated with State-Trait Anxiety Inventory-trait anxiety (r = 0.25, P = 0.046) and Basic Psychological Need Satisfaction and Frustration Scale-autonomy frustration scores (r = 0.29, P = 0.018). Patients with abnormally high cerebrospinal fluid interleukin-6 levels (defined >97.5 percentile of the controls) had higher scores for trait anxiety (P = 0.035) and autonomy frustration (P = 0.026), and significantly increased regional cerebral blood flow in the left superior temporal gyrus, bilateral nucleus accumbens, and cerebellum than the remaining patients. Patients with elevated cerebrospinal fluid interleukin-6 constitute a subpopulation of psychiatric disorders associated with anxiety and autonomy frustration, which may be related to altered functions in specific brain areas.

Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs. Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89–123.31 vs Non-Pronounced 6.22, CI 2.9–13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.

Diagnostic, monitoring, and prognostic value of combined detection of cerebrospinal fluid heparin-binding protein, interleukin-6, interleukin-10, and procalcitonin for post-neurosurgical intracranial infection

ObjectiveIntracranial infection is a common complication after neurosurgery and can increase the length of hospital stay, affect patient prognosis, and increase mortality. We aimed to investigate the value of the combined detection of cerebrospinal fluid (CSF) heparin-binding protein (HBP), interleukin-6 (IL-6), interleukin-10 (IL-10), and procalcitonin (PCT) for post-neurosurgical intracranial infection. MethodsThis study assessed the diagnostic values of CSF HBP, IL-6, IL-10, PCT levels, and combined assays for post-neurosurgical intracranial infection with the area under the receiver operating characteristic (ROC) curve by retrospectively analysing biomarkers of post-neurosurgical patients. ResultsThe CSF HBP, IL-6, IL-10, and PCT levels were significantly higher in the infected group than the uninfected group and the control group (P < 0.001). The indicators in the groups with severe intracranial infections were significantly higher than those in the groups with mild intracranial infections (P < 0.001), and the groups with poor prognoses had significantly higher indexes than the groups with good prognoses. According to the ROC curve display, the AUC values of CSF HBP, IL-6, IL-10, and PCT were 0.977 (95 % CI 0.952–1.000), 0.973 (95 % CI 0.949–0.998), 0.884 (95 % CI 0.823–0.946), and 0.819 (95 % CI 0.733–0.904), respectively. The AUC of the combined test was 0.996 (95 % CI 0.989–1.000), which was higher than those of the four indicators alone. ConclusionThe combined detection can be an important indicator for the diagnosis and disease monitoring of post-neurosurgical intracranial infection.

Abstract WP152: Association Between Cerebrospinal Fluid Interleukin-6 Levels and Cerebral Autoregulation After Aneurysmal Subarachnoid Hemorrhage

Introduction: Elevated levels of Interleukin-6 (IL-6) levels in cerebrospinal fluid (CSF) have been correlated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, the role of neuroinflammation in SAH pathophysiology remains incompletely understood. In a pig stroke model, IL-6 antagonist prevented hypotension-induced pial artery impairment, suggesting a role in post-stroke vascular derangement. This research assesses serial CSF IL-6 levels' relationship with cerebral autoregulation in aSAH patients. Methods: We prospectively enrolled aSAH patients at Yale-New Haven Hospital. Autoregulatory function was measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation response to changes in mean arterial pressure (MAP). The resulting autoregulatory index was used to trend the MAP range at which autoregulation was most preserved. Percent time that MAP exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. IL-6 levels were assessed through serial CSF samples and correlated with hemodynamic parameters. Results: We calculated limits of autoregulation for twenty-two patients (mean age 60 ± 9 years, mean Hunt Hess score 3.4 ± 1.2, mean modified Fisher score 3.7 ± 0.58, average monitoring time 10.1 ± 7.3 hours). Optimal MAP and limits were calculated an average of 74% ± 20% of monitoring time. Our study provides preliminary support for a potential association between IL-6 levels and percent time that MAP was within limits of autoregulation (b = -0.31, p=0.009, Fig. 1A). Additionally, there was a significant correlation between IL-6 levels and the extent to which MAP deviated from computed optimal MAP (r= 0.636, p=0.009, Fig. 1B). Conclusions: IL-6 may contribute to impaired autoregulation post aSAH. Further studies are needed to validate findings and refine MAP management for improved outcomes in aSAH patients.

Rheumatoid meningitis: a rare neurological complication of rheumatoid arthritis.

To describe the clinical and neuroimaging characteristics of rheumatoid meningitis (RM) in Chinese patients. The patients admitted to our hospital with the diagnosis of RM in the past 8 years were retrospectively analyzed. Six patients with RM were identified among 933 patients admitted with rheumatoid arthritis (RA). The symptoms of meningitis occurred after onset of arthritis in five patients and before onset in one. Headache (n=6), hyperacute focal neurological deficits (n=4) and seizures (n=3) were the most prevalent symptoms. The nadir modified Rankin Scale score was ≥3 in five patients. Rheumatoid factor was elevated in all patients, and interleukin-6 levels in cerebrospinal fluid were dramatically elevated in three of four tested patients. Magnetic resonance imaging of the brain revealed that the meninges were affected in all patients and the cerebral parenchyma was affected in one patient. The lesions were generally located in the frontoparietal region and showed restricted diffusion along the adjacent subarachnoid space. RM occurred during disease-modifying therapy in four patients. In the acute episode, three patients improved on tocilizumab and the other three improved on pulse corticosteroids. For maintenance therapy, two patients received combined therapy of tocilizumab and other immunosuppressive agents, one received adalimumab and methotrexate, and two received low-dose oral corticosteroids with an immunosuppressive agent. Five patients had a good outcome, and one died of Pneumocystis jirovecii pneumonia after stabilization of his neurologic conditions. No relapse of RM occurred on immunotherapy during follow-up. Chinese patients with RM share some remarkable clinical and neuroimaging features and respond well to appropriate immunotherapy. Tocilizumab could be a treatment option for this severe complication of RA.

Elevated brain derived neurotrophic factor in plasma and interleukin-6 levels in cerebrospinal fluid in meningitis compared to cerebral malaria

Neurological infections, such as Cerebral malaria (CM) and meningitis are associated with high mortality and in survivors, particularly young children, persistent neurologic deficits often remain. As brain inflammation plays a role in the development of these neurological sequelae, multiplex assays were used to assess a select set of immune mediators in both plasma and cerebrospinal fluid (CSF) from Zambian children with neurological infections.Both CM and meningitis patients showed high levels of markers for vascular inflammation, such as soluble ICAM-1 and angiopoietins. Although high levels of angiopoietin 1 and angiopoietin 2 were found in the meningitis group, their levels in the CSF were low and did not differ.As expected, there were high levels of cytokines and notably a significantly elevated IL-6 level in the CSF of the meningitis group. Interestingly, although elevated levels BDNF were found, BDNF levels were significantly higher in plasma of the meningitis group but similar in the CSF.The striking differences in plasma BDNF and IL-6 levels in the CSF point to markedly different neuro-pathological processes. Therefore, further investigations in the role of both IL-6 and BDNF in the neurological outcomes are needed.

Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD

Lymphatic drainage in the central nervous system is regulated by meningeal lymphatic vasculature, and recurrent neuroinflammation alters lymphatic vessel remodeling. Patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) were reported to demonstrate worse outcomes compared with patients with anti-myelin oligodendrocyte glycoprotein-associated disorders (MOGAD). This study aimed to investigate the serum cytokines relevant to vascular remodeling after attacks and their prognostic role in patients with AQP4 + NMOSD. This study measured the serum levels of 12 cytokines relevant to vascular remodeling, including bone morphogenetic protein-9 (BMP-9) and leptin, in 20 patients with AQP4 + NMOSD and 17 healthy controls (HCs). Disease controls included 18 patients with MOGAD. Serum and cerebrospinal fluid interleukin-6 levels were also measured. Clinical severity was evaluated with Kurtzke’s Expanded Disability Status Scale (EDSS). Compared with HCs, patients with AQP4 + NMOSD showed higher BMP-9 (median; 127 vs. 80.7 pg/mL; P = 0.0499) and leptin levels (median; 16,081 vs. 6770 pg/mL; P = 0.0224), but not those with MOGAD. Better improvement in EDSS at 6 months was associated with baseline BMP-9 levels in patients with AQP4 + NMOSD (Spearman’s rho = − 0.47; P = 0.037). Serum BMP-9 is upregulated at relapse and may contribute to vascular remodeling in AQP4 + NMOSD. Serum BMP-9 levels could predict clinical recovery 6 months after the attack.

Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma

To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ［ (5.78±2.69) pg/ ml］ and CXCL-13 ［(0.83±0.59) pg/ml］ in protein elevated group were significantly higher than those in the protein normal group ［IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/ml］ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

Cerebrospinal Fluid Interleukin-10 Biomarker for Vitreoretinal Lymphoma

To analyze the correlation between cerebrospinal fluid (CSF) interleukin-10 (IL-10) levels and the clinical characteristics in patients with vitreoretinal lymphoma (VRL). Retrospective observational case series. Forty-one patients were diagnosed as VRL and underwent lumbar puncture for CSF examination. Aqueous humor cytokine detection, vitreous cytopathologic analysis, monoclonal gene rearrangement, and flow cytometry were performed. The CSF was assessed through biochemical and cytologic examination, flow cytometry, and cytokine detection. The median levels of aqueous humor IL-10 and IL-6 were 415.0 and 40.7 pg/mL. The median CSF levels of IL-10 and IL-6 were 35.7 and 3.5 pg/mL, respectively. IL-10 levels in CSF were higher than normal in 37 patients (90.2%) and higher in patients with intracranial lesions. The level of CSF IL-10 decreased after systemic treatment, and it rose before intracranial lesion onset or recurrence. The level of IL-10 in CSF was related to the duration of ocular symptoms, but was not related to the level of IL-10 in aqueous humor. There was no significant difference in CSF IL-10 levels between patients with and without anterior chamber inflammation or retinal lesions. In eyes with recurrent vitreoretinal lymphoma, the level of IL-10 in aqueous humor increased significantly, but there was no corresponding increase in the level of IL-10 in CSF. CSF IL-10 is a potentially important biomarker in VRL, especially in the monitoring of intracranial lesions.

Fatigue in Multiple Sclerosis Is Associated with Reduced Expression of Interleukin-10 and Worse Prospective Disease Activity.

In multiple sclerosis (MS), fatigue is a frequent symptom that negatively affects quality of life. The pathogenesis of fatigue is multifactorial and inflammation may play a specific role. To explore the association between fatigue, central inflammation and disease course in MS in 106 relapsing-remitting (RR)-MS patients, clinical characteristics, including fatigue and mood, were explored at the time of diagnosis. NEDA (no evidence of disease activity)-3 status after one-year follow up was calculated. Cerebrospinal fluid (CSF) levels of a set of proinflammatory and anti-inflammatory molecules and peripheral blood markers of inflammation were also analyzed. MRI structural measures were explored in 35 patients. A significant negative correlation was found at diagnosis between fatigue measured with the Modified Fatigue Impact Scale (MFIS) and the CSF levels of interleukin (IL)-10. Conversely, no significant associations were found with peripheral markers of inflammation. Higher MFIS scores were associated with reduced probability to reach NEDA-3 status after 1-year follow up. Finally, T2 lesion load showed a positive correlation with MFIS scores and a negative correlation with CSF IL-10 levels at diagnosis. CSF inflammation, and particularly the reduced expression of the anti-inflammatory molecule IL-10, may exacerbate fatigue. Fatigue in MS may reflect subclinical CSF inflammation, predisposing to greater disease activity.

Encephalitis with status epilepticus and stroke as complications of non-severe COVID-19 in a young female patient: a case report

BackgroundNeurological manifestations of COVID-19 are thought to be associated with the disease severity of COVID-19 and poor clinical outcomes. Dysregulated immune responses are considered to be mediating such complications. Our case illustrates multiple critical neurological complications simultaneously developed in a patient with non-severe COVID-19 and successful recovery with a multifaceted therapeutic approach. The cerebrospinal fluid (CSF) interleukin-6 (IL-6) level was temporally correlated with the clinical severity of the status epilepticus in our patient, suggesting a causal relationship.Case presentationA previously healthy 20-year-old female patient presented with a first-onset seizure. Concomitant non-severe COVID-19 pneumonia was diagnosed. CSF study showed lymphocytic pleocytosis with elevated IL-6 levels in CSF. During hospitalization under the diagnosis of autoimmune encephalitis, status epilepticus developed, and the seizure frequency was temporally correlated with the CSF IL-6 level. Furthermore, a new embolic stroke developed without a significant cardioembolic source. Contrary to the exacerbated COVID-19-associated neurological complications, COVID-19 pneumonia was cleared entirely. After treatment with antiseizure medications, antithrombotics, antiviral agents, and immunotherapy, the patient was discharged with near-complete recovery.ConclusionActive serological, and radiological evaluation can be helpful even in non-severe COVID-19, and multidimensional treatment strategies, including immunotherapy, can successfully reverse the neurological complication.

CSF lipocalin-2 increases early in subarachnoid hemorrhage are associated with neuroinflammation and unfavorable outcome

Lipocalin-2 mediates neuro-inflammation and iron homeostasis in vascular injuries of the central nervous system (CNS) and is upregulated in extra-CNS systemic inflammation. We postulate that cerebrospinal fluid (CSF) and blood lipocalin-2 levels are associated with markers of inflammation and functional outcome in subarachnoid hemorrhage (SAH). We prospectively enrolled 67 SAH subjects, serially measured CSF and plasma lipocalin-2, matrix metallopeptidase 9 (MMP-9), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) on post-SAH days 1-5 and assessed outcome by modified Rankin Scale (mRS) every 3 months. Unfavorable outcome is defined as mRS > 2. Twenty non-SAH patients undergoing lumbar drain trial were enrolled as controls. Lipocalin-2 was detectable in the CSF and significantly higher in SAH compared to controls (p < 0.0001). Higher CSF LCN2 throughout post-SAH days 1-5 was associated with unfavorable outcome at 3 (p = 0.0031) and 6 months (p = 0.014). Specifically, higher CSF lipocalin-2 on post-SAH days 3 (p = 0.036) and 5 (p = 0.016) were associated with unfavorable 3-month outcome. CSF lipocalin-2 levels positively correlated with CSF IL-6, TNF-α and MMP-9 levels. Higher plasma lipocalin-2 levels over time were associated with worse 6-month outcome. Additional studies are required to understand the role of lipocalin-2 in SAH and to validate CSF lipocalin-2 as a potential biomarker for SAH outcome.

CSF interleukin 6 is a useful marker to distinguish pseudotumoral CNS inflammatory diseases from primary CNS lymphoma.

Interleukin6 (IL-6) is a pleomorphic cytokine that can be found in the cerebrospinal fluid (CSF) in a wide spectrum of inflammatory pathologies of the central nervous system (CNS). Our aim was to characterize the diagnostic significance of CSF IL-6 among various CNS inflammatory diseases with pseudotumoral lesions (CNSID) and primary CNS lymphoma (PCNSL). We retrospectively analyzed the CSF IL-6 concentrations in 43 consecutive patients with suspected PCNSL. A total of 28 patients were positively diagnosed with PCNSL and 15 with CNSID. We verified the results with CSF IL-10, an established biomarker for PCNSL. In the PCNSL group, the median CSF IL-6 concentration was 8pg/ml, interquartile range (IQR) 5-18.5. For the patients with CNSID, the median concentration was 70pg/ml, IQR 5-1368. A group comparison showed significantly higher CSF IL-6 levels in patients with CNSID than in those with PCNSL (p = 0.032). Moreover, IL-6 was correlated with CSF cell count in the CNSID group (r = 0.56, p = 0.028), but not in the PCNSL group (r = 0.3, p = 0.13). We found significantly higher CSF IL-10 levels in patients with PCNSL than in patients with CNS inflammatory lesions (p < 0.001). Our study suggests that CSF IL-6 levels could represent, in addition to CSF IL-10, a useful biomarker in the differential diagnosis of CNSID and suspected PCNSL.

Interleukin 6 in cerebrospinal fluid is a biomarker for delayed cerebral ischemia (DCI) related infarctions after aneurysmal subarachnoid hemorrhage

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine and has been discussed as a potential biomarker for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage. In the present study we have analyzed the time course of serum and cerebrospinal fluid (CSF) IL-6 levels in 82 patients with severe aneurysmal subarachnoid hemorrhage (SAH) requiring external ventricular drains in correlation to angiographic vasospasm, delayed cerebral ischemia, secondary infarctions and other clinical parameters. We observed much higher daily mean IL-6 levels (but also large interindividual variations) in the CSF than the serum of the patients with a peak between days 4 and 14 including a maximum on day 5 after SAH. Individual CSF peak levels correlated significantly with DCI (mean day 4–14 peak, DCI: 26,291 ± 24,159 pg/ml vs. no DCI: 16,184 ± 13,163 pg/ml; P = 0.023). Importantly, CSF IL-6 levels differed significantly between cases with DCI and infarctions and patients with DCI and no infarction (mean day 4–14 peak, DCI with infarction: 37,209 ± 26,951 pg/ml vs. DCI, no infarction: 15,123 ± 11,239 pg/ml; P = 0.003), while findings in the latter patient group were similar to cases with no vasospasm (mean day 4–14 peak, DCI, no infarction: 15,123 ± 11,239 vs. no DCI: 15,840 ± 12,979; P = 0.873). Together, these data support a potential role for elevated CSF IL-6 levels as a biomarker for DCI with infarction rather than for DCI in general. This fits well with a growing body of evidence linking neuroinflammation to ischemia and infarction, but (together with the large interindividual variations observed) limits the diagnostic usefulness of CSF IL-6 levels in SAH patients.

Role of Serum IL-6 in Neuropsychiatric Systemic lupus Erythematosus.

ObjectiveThe present study was designed in order to elucidate the roles of serum interleukin 6 (IL‐6) in the pathogenesis in neuropsychiatric systemic lupus erythematosus (NPSLE).MethodsPaired serum and cerebrospinal fluid (CSF) samples were obtained from 101 patients with SLE when they presented active neuropsychiatric manifestations (69 patients with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 32 patients with neurologic syndromes or peripheral nervous system involvement [focal NPSLE]) and from 22 control patients without SLE with noninflammatory neurological diseases. The levels of albumin and IL‐6 in CSF and sera were measured by enzyme‐linked immunosorbent assay.ResultsSerum IL‐6 and CSF IL‐6 were elevated in NPSLE compared with non‐SLE controls. Among NPSLE, serum IL‐6 and CSF IL‐6 were significantly elevated in acute confusional state (ACS) compared with non‐ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder, and psychosis) or focal NPSLE. Q albumin (CSF/serum albumin quotient) was also significantly higher in ACS than in the other two groups of NPSLE. Of note, serum IL‐6 (r = 0.2801, p = 0.0207), but not CSF IL‐6 (r = 0.1602, p = 0.1918), was significantly correlated with Q albumin in patients with diffuse NPSLE, including ACS and non‐ACS.ConclusionThese results indicate that serum IL‐6 as well as CSF IL‐6 is involved in the pathogenesis of NPSLE. Moreover, it is suggested that serum IL‐6 might play a most important role in blood‐brain barrier breakdown in NPSLE.

Postinfectious inflammation in cerebrospinal fluid is associated with nonconvulsive seizures in subarachnoid hemorrhage patients

PurposeIt was unclear how nonconvulsive seizures (NCS) occurred after subarachnoid hemorrhage (SAH). The aim of this prospective observational study was to determine the association between cerebrospinal fluid postinfectious inflammation and NCS in patients with SAH. MethodsDemographics and parameters were retrieved from pooled data of all SAH patients monitored by continuous electroencephalography (cEEG) in our Stroke-Intensive Care Unit (Stroke-ICU) over six years period. Patients were divided into two groups (NCS group and non-NCS group). According to clinical and cerebrospinal fluid (CSF) parameters, a logistic regression model was used to analyze the association between CSF inflammation and NCS. ResultsThe data of 143 SAH patients were analyzed (25 patients with NCS and 118 patients with non-NCS). Median age was 53 years (min – max: 19 years – 90 years). 4.8 % SAH patients were accompanied with NCS. Among these 25 NCS patients, only 2 (8%) had complete control of EEG discharges. After confounders correction, logistic regression analysis showed: SAH patients with older age [P = 0.003, OR = 1.193, 95 %CI (1.062–1.341)], intracranial infections [P = 0.000, OR = 171.939, 95 %CI (18.136–1630.064)] and higher increased modified Fisher Scale (mFS) [P = 0.003, OR = 8.884, 95 %CI (2.125–37.148)] were more likely to develop NCS; furthermore, a high level of CSF interleukin-6 (IL-6) was an independent risk factor for NCS [P = 0.000, OR = 1.015, 95 %CI (1.010–1.020)], with a threshold of 164.9 pg/mL (sensitivity = 0.84, specificity = 0.96). Compared with non-NCS patients, NCS patients were more likely to have poor Glasgow outcome scale (GOS) (1–3) at 3 months after discharge (88 %). ConclusionsSAH patients with NCS were associated with poor neurological prognosis. With the increase of age and mFS, these patients were more likely to develop NCS. As an intracranial infective mark, a high level of CSF IL-6 was an independent risk factor for NCS. For brain protection of severe brain injury after SAH, we should focus on the increasingly important role of inflammatory response.

Composite contributions of cerebrospinal fluid GABAergic neurosteroids, neuropeptide Y and interleukin-6 to PTSD symptom severity in men with PTSD

Given that multiple neurobiological systems, as well as components within these systems are impacted by stress, and may interact in additive, compensatory and synergistic ways to promote or mitigate PTSD risk, severity, and recovery, we thought that it would be important to consider the collective, as well as separate effects of these neurobiological systems on PTSD risk. With this goal in mind, we conducted a proof-of-concept study utilizing cerebrospinal fluid (CSF) collected from unmedicated, tobacco- and illicit substance-free men with PTSD (n = 13) and trauma-exposed healthy controls (TC) (n = 17). Thirteen neurobiological factors thought to contribute to PTSD risk or severity based on previous studies were assayed. As the small but typical sample size of this lumbar puncture study limited the number of factors that could be considered in a hierarchical regression model, we included only those five factors with at least a moderate correlation (Spearman rho > 0.30) with total Clinician-Administered PTSD Scale (CAPS-IV) scores, and that did not violate multicollinearity criteria. Three of the five factors meeting these criteria—CSF allopregnanolone and pregnanolone (Allo + PA: equipotent GABAergic metabolites of progesterone), neuropeptide Y (NPY), and interleukin-6 (IL-6)—were found to account for over 75% of the variance in the CAPS-IV scores (R2 = 0.766, F = 8.75, p = 0.007). CSF Allo + PA levels were negatively associated with PTSD severity (β = −0.523, p = 0.02) and accounted for 47% of the variance in CAPS-IV scores. CSF NPY was positively associated with PTSD severity (β = 0.410, p = 0.04) and accounted for 14.7% of the CAPS-IV variance. There was a trend for a positive association between PTSD severity and CSF IL-6 levels, which accounted for 15.3% of the variance in PTSD severity (β = 0.423, p = 0.05). Z-scores were then computed for each of the three predictive factors and used to depict the varying relative degrees to which each contributed to PTSD severity at the individual PTSD patient level. This first of its kind, proof-of-concept study bears replication in larger samples. However, it highlights the collective effects of dysregulated neurobiological systems on PTSD symptom severity and the heterogeneity of potential biological treatment targets across individual PTSD patients—thus supporting the need for precision medicine approaches to treatment development and prescribing in PTSD.

Tumor-associated macrophage related interleukin-6 in cerebrospinal fluid as a prognostic marker for glioblastoma

Interleukin-6 (IL-6) is one of the pleiotropic cytokines and has received attention as a critical factor implicated in the invasion and the angiogenesis of various cancers. In glioma, IL-6 is known to be associated with the prognosis; however, the roles of IL-6 in cerebrospinal fluid (CSF) has not been studied sufficiently. We examined the concentration of CSF IL-6 using 75 CSF samples of glioma (54 glioblastomas (GBMs) and 21 other grades of gliomas) and analyzed the association CSF IL-6 with infiltration levels of tumor-associated macrophages (TAMs) and prognosis. The concentration of CSF IL-6 in GBM patients was significantly higher than that in other grades of gliomas. CSF IL-6 levels were associated with the infiltration rate of TAMs in GBMs, and IL-6 levels were increased in the GBM cells co-cultured with TAM-like macrophages. The CSF of GBM patients, which contained high concentration of IL-6, promoted the migration ability of GBM cells, and neutralization antibodies of IL-6 inhibited its migration ability. Finally, in both univariate and multivariate analysis, higher CSF IL-6 levels were associated with poorer prognosis in GBM patients. These results indicated that the concentration of CSF IL-6 is associated with TAMs’ infiltration level and may be a useful prognostic biomarker for the GBM patients.

Clinical characteristics and cerebro-spinal fluid cytokine changes in patients with acquired immunodeficiency syndrome and central nervous system infection.

Clinical characteristics and the cerebro-spinal fluid (CSF) cytokine changes in acquired immunodeficiency syndrome (AIDS) patients with tuberculous meningitis and cryptococcal meningitis in central nervous system (CNS) infections before and after treatment were investigated. The clinical records of 80 AIDS patients with CNS infections and 40 non-CNS infection patients hospitalized in the Infection Department of the First Hospital of Changsha from February 2013 to March 2016 were retrospectively analyzed. Forty-one cases of AIDS complicated with tuberculous meningitis were enrolled as group A, 39 cases of AIDS complicated with cryptococcal meningitis as group B, and 40 cases of non-CNS infection with lumbar puncture indication as group C. The general data, clinical symptoms, CSF examination and prognosis of the three groups of patients were collected. Of the 80 patients, 56 patients were discharged from hospital (improvement group) and 24 died (death group) after treatment. The concentrations of interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in CSF were detected by enzyme-linked immunosorbent assay. There were significant differences in clinical manifestations, CSF pressure, CSF leucocyte count, CSF glucose, CSF chloride and CSF protein between group A, group B and group C (P<0.05). The concentrations of IFN-γ, IL-6, IL-10 and TNF-α in CSF of group A and group B increased significantly compared with group C (P<0.001). The IL-6, IL-10 and TNF-α levels in CSF in the improvement group were significantly lower than those in the death group (P<0.001), while the concentration of IFN-γ increased significantly (P<0.001). CSF biochemistry is characterized by increased pressure, leucocyte count and protein, and decreased chloride and glucose. IFN-γ, IL-6, IL-10 and TNF-α in CSF have certain predictive value for poor prognosis of AIDS patients with CNS infection.