interleukin-8 and Spinal-Cord-Injuries

There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would be facilitated by the availability of biomarkers with which to stratify injury severity and predict neurological recovery. Cerebrospinal fluid (CSF) samples were obtained over a period of 72 h in 27 patients with complete SCI (ASIA A) or incomplete SCI (ASIA B or C). Cytokines were measured in CSF and serum samples using a multiplex cytokine array system and standard enzyme-linked immunosorbent assay (ELISA) techniques. Neurological recovery was monitored, and patient-reported neuropathic pain was documented. IL-6, IL-8, MCP-1, tau, S100beta, and glial fibrillary acidic protein (GFAP) were elevated in a severity-dependent fashion. A biochemical model was established using S100beta, GFAP, and IL-8 to predict injury severity (ASIA A, B, or C). Using these protein concentrations at 24-h post injury, the model accurately predicted the observed ASIA grade in 89% of patients. Furthermore, segmental motor recovery at 6 months post injury was better predicted by these CSF proteins than with the patients' baseline ASIA grade. The pattern of expression over the first 3 to 4 days post injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1 provides invaluable information about the pathophysiology of human SCI. A prediction model that could use such biological data to stratify injury severity and predict neurological outcome may be extremely useful for facilitating the clinical validation of novel treatments in acute human SCI.

Topics: Adult; Biomarkers; Chemokine CCL2; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Glial Fibrillary Acidic Protein; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Myelitis; Nerve Growth Factors; Predictive Value of Tests; Prognosis; Prospective Studies; Recovery of Function; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Spinal Cord; Spinal Cord Injuries; tau Proteins; Trauma Severity Indices; Young Adult

Emerging evidence has manifested that many microRNAs (miRNAs) exert crucial roles in the responses and remission process of traumatic spinal cord injury (TSCI). The present study aimed to investigate clinical significance of miR-34a concerning the assessment of neurological remission and prognosis after TSCI.. We examined the serum levels of miR-34a in patients with TSCI and healthy controls through real-time polymerase chain reaction (RT-qPCR) assay. Then, receiver operating characteristic (ROC) curve was used to determine the diagnostic value of miR-34a in TSCI. Finally, we detected the expression levels of miR-34a from serum samples over a 12-week period.. The results of our study demonstrated that miR-34a was significantly down-regulated in TSCI patients compared with healthy controls. miR-34a may function a potential biomarker for TSCI diagnosis with an area under curve (AUC) of 0.8020. The expression of miR-34a was increased in the remission group compared to the non-remission group after 12 weeks post-injury. The expression of miR-34a was negatively related to TNF-alpha, IL-6, and IL-8.. Measuring serum expression level of miR-34a over time may be used in tracking the process and neurological remission of TSCI.

Topics: Biomarkers; Down-Regulation; Gene Expression; Humans; Interleukin-6; Interleukin-8; MicroRNAs; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; ROC Curve; Spinal Cord Injuries; Time Factors; Tumor Necrosis Factor-alpha; Wounds and Injuries

Topics: Adaptive Immunity; Animals; Disease Models, Animal; Down-Regulation; Forelimb; Humans; Immunity, Innate; Inflammation; Interleukin-6; Interleukin-8; Luciferases; Mice; MicroRNAs; Molecular Mimicry; Muscle Strength; Recovery of Function; RNA, Messenger; Spinal Cord Injuries; Time Factors; TNF Receptor-Associated Factor 6

The dysfunctional sympathetic nervous system in individuals with cervical spinal cord injury (CSCI) impairs adrenergic responses and may, therefore, contribute to the blunted post-exercise cytokine response. The purpose of this study was to investigate an alternative way to exercise to induce an acute cytokine response by passive core temperature elevation in CSCI.. Seven male participants with a motor complete CSCI and 8 male able-bodied controls were immersed for 60 min in water set at a temperature 2 °C above the individuals' resting oesophageal temperature. Blood was collected pre, post, and every hour up to 4 h post-immersion.. Hot water immersion resulted in an IL-6 plasma concentration mean increase of 133 ± 144 % in both groups (P = 0.001). On a group level, IL-6 plasma concentrations were 68 ± 38 % higher in CSCI (P = 0.06). In both groups, IL-8 increased by 14 ± 11 % (P = 0.02) and IL-1ra by 18 ± 17 % (P = 0.05). Catecholamine plasma concentrations were significantly reduced in CSCI (P < 0.05) and did not increase following immersion.. Passive elevation of core temperature acutely elevates IL-6, IL-8 and IL-1ra in CSCI despite a blunted adrenergic response, which is in contrast to earlier exercise interventions in CSCI. The present study lays the foundation for future studies to explore water immersion as an alternative to exercise to induce an acute cytokine response in CSCI.

Topics: Adult; Catecholamines; Cervical Cord; Hot Temperature; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Interleukin-8; Male; Middle Aged; Spinal Cord Injuries; Time Factors

Interleukins are a group of cytokines responsible for regulating inflammatory and infectious responses. Interleukin-8 plays an important role in chemotaxis and functioning of leukocytes and is locally produced in infected tissues; it is seen in abundance in the urine of individuals with Urinary Tract Infection.. Midstream sterile urine sampling was performed in different patients admitted to the Spinal Cord Injury (SCI) research center. The samples were tested to determine the level of IL-8 through the ELISA method. The commercial kit used for this study was an R & D kit built in Germany.. The mean level of IL-8 was 369.59 pg/ml and 75.42 pg/ml in male and female patients respectively. Among the 97 patients under study, 87 (89.7%) were IL-8 positive (>10 pg/ml) and 10 patients were IL-8 negative (<10 pg/ml). Among the 87 IL-8 positive subjects, 64 patients had no UTI symptoms, while 23 did.. SCI patients should have their urinary IL-8 levels measured on a routine and periodic basis, irrespective of their SCI severity or the presence or absence of UTI symptoms. The timely and effective diagnosis & treatment of UTI can prevent the irreversible complications caused by frequent UTI and resistance to treatment in this group of patients.

Topics: Adult; Asymptomatic Infections; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Spinal Cord Injuries; Urinary Tract Infections; Young Adult

Topics: Accidents, Occupational; Adult; Biomarkers; Electric Injuries; Follow-Up Studies; Humans; Interleukin-8; Male; Paraplegia; Spinal Cord Injuries

To determine the serum cytokine profiles of patients with spinal cord injury (SCI) and varying clinical presentations relative to healthy, able-bodied, age-matched control subjects.. Cross-sectional study.. Clinical research unit.. People with SCI (N=56) and different clinical presentations, and healthy, able-bodied, age-matched control subjects (N=35).. Not applicable.. Serum levels of the proinflammatory cytokines interleukin (IL) 1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), the anti-inflammatory cytokines IL-4 and IL-10, the regulatory cytokine IL-2, the IL-1 receptor antagonist (IL-1RA), and autoantibodies against myelin-associated glycoprotein and GM(1) ganglioside (anti-GM(1)) immunoglobulin (IgG and IgM), as determined by enzyme-linked immunosorbent assay. The relationship between elevated serum cytokine levels and clinical variables was also studied.. SCI subjects exhibited serum concentrations of IL-6, TNF-alpha, IL-1RA, and anti-GM(1) (IgG) that were greater (P<.05) than control group values. Elevated cytokine concentrations were not associated with high white blood cell counts, level of injury, or American Spinal Injury Association classification; they were evident in SCI subjects who were asymptomatic for medical complications, but were further elevated in subjects with pain, urinary tract infection (UTI), and pressure ulcers.. Elevated levels of circulating proinflammatory cytokines and autoantibodies are present in the serum of SCI subjects without medical complications, and are further elevated in SCI subjects with neuropathic pain, UTI, or pressure ulcers, relative to healthy, able-bodied control subjects. These findings may be indicative of a protective autoimmunity, simply a consequence of occult or evident infection, or evidence of cytokine dysregulation that may contribute to an immune-mediated impairment of axonal conduction.

Topics: Adult; Autoantibodies; Cervical Vertebrae; Cross-Sectional Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Male; Myelin-Associated Glycoprotein; Paraplegia; Pressure Ulcer; Quadriplegia; Reference Values; Spinal Cord Injuries; Thoracic Vertebrae; Tumor Necrosis Factor-alpha; Urinary Tract Infections

Antithrombin (AT) reveals its antiinflammatory activity by promoting endothelial release of prostacyclin (PGI(2)) in vivo. Since neuroinflammation is critically involved in the development of ischemia/reperfusion (I/R)-induced spinal cord injury (SCI), it is possible that AT reduces the I/R-induced SCI by attenuating the inflammatory responses. We examined this possibility using rat model of I/R-induced SCI in the present study. AT significantly reduced the mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. Microinfarctions of the spinal cord seen after reperfusion were markedly reduced by AT. AT significantly enhanced the I/R-induced increases in spinal cord tissue levels of 6-keto-PGFIalpha, a stable metabolite of PGI2. AT significantly inhibited the I/R-induced increases in spinal cord tissue levels of TNF-alpha, rat interleukin-8 and myeloperoxidase. In contrast,Trp(49) -modified AT did not show any protective effects. Pretreatment with indomethacin significantly reversed the protective effects of AT. An inactive derivative of factor Xa, which selectively inhibits thrombin generation, has been shown to fail to reduce SCI. Taken together, these observations strongly suggested that AT might reduce I/R-induced SCI mainly by the antiinflammatory effect through promotion of endothelial production of PGI(2). These findings also suggested that AT might be a potential neuroprotective agent.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antithrombins; Coloring Agents; Disease Models, Animal; Epoprostenol; Factor Xa; Humans; Inflammation; Interleukin-8; Ischemia; Male; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Spinal Cord; Spinal Cord Injuries; Tetrazolium Salts; Time Factors; Tryptophan; Tumor Necrosis Factor-alpha

In view of a cytoprotective effect of elastase inhibitor on chemokine-mediated tissue injury, we examined the neuroprotective effect of ONO-5046, a specific inhibitor of neutrophil elastase, in rats with spinal cord injury. Standardized spinal cord compression markedly increased cytokine-induced neutrophil chemo-attractant (CINC)-1 mRNA and protein. Their increases correlated with neurologic severity of injured rats. Immunohistochemically, CINC-1 protein was detected sequentially in vascular endothelial cells at 4 h, in perivascular neutrophils at 8 h, and in neutrophils infiltrating into cord substance at 12 h. Pretreatment with ONO-5046 (50 mg/kg) markedly ameliorated motor disturbance in injured rats, and reduced CINC-1 protein and mRNA expression. ONO-5046 also significantly reduced the increase of neutrophil accumulation or infiltration estimated by myeloperoxidase activity, and the extent of vascular permeability by Evans blue extravasation in the injured cord segment in comparison to control animals receiving vehicle. These results suggest that CINC-1 contributed to inflammation in rat spinal cord injury and ONO-5046 attenuated neurologic damage partly by blocking CINC-1 production of the chemoattractant, preventing neutrophil activation and vascular endothelial cell injury.

Topics: Animals; Blood-Brain Barrier; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Gene Expression; Glycine; Growth Substances; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Interleukin-8; Leukocyte Elastase; Motor Activity; Peroxidase; Rats; Rats, Wistar; Recovery of Function; RNA, Messenger; Serine Proteinase Inhibitors; Spinal Cord; Spinal Cord Injuries; Sulfonamides

21-aminosteroids (lazaroids) have demonstrated the protective effect against cerebral ischemic injury through the inhibition of lipid peroxidation. We examined whether lazaroids affected the production of proinflammatory and antiinflammatory cytokines in ischemic spinal cord injury model.. Anesthetized New Zealand white rabbits underwent a 20-minute infrarenal aortic cross-clamping (AXC) with pretreatment of either an intravenous 3 mg/kg lazaroid U74389G (group L; n = 10) or the same volume saline (group P; n = 10). Sham operation group (group S; n = 6) underwent only exposure of the aorta. Plasma concentrations of interleukin (IL)-8, -1beta, -1 receptor antagonist (IL-1ra) and tumor necrosis factor (TNF)-alpha were measured at four time points. Functional assessment with Tarlov score at 24 and 48 hours after pretreatment, pathologic assessment of the spinal cord, and measurements of cytokine levels in the spinal cord were performed.. The maximum elevation of plasma IL-8 and -1ra levels occurred at 1 hour after declamping in four measurement points. Plasma IL-8 and -1ra levels in group L were significantly lower than those in group P (*p < 0.05). Plasma TNFalpha peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNFalpha levels were not different among three groups. Spinal IL-8 levels in group L (0.98 +/- 0.34 ng/g tissue) were lower than those in group P (7.26 +/- 2.26 ng/g tissue)(*p < 0.05). Spinal IL-1ra and TNFalpha were not significantly different. Tarlov score and pathologic assessment were better in group L.. Lazaroid U-74389G reduced the production of systemic IL-8 and -1ra and spinal IL-8 when AXC caused spinal cord injury. These results indicate that lazaroids may attenuate ischemic endothelial cell injury or activation of leukocytes.

Topics: Animals; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Ischemia; Neuroprotective Agents; Pregnatrienes; Rabbits; Receptors, Interleukin-1; Sialoglycoproteins; Spinal Cord Injuries