Correlation Between Chemokine Production and Injury Type in Acute Brain Injury Patients

ABSTRACT

PURPOSE: Cytokines and chemokines are essential in neuronal development and play important roles in both acute and chronic inflammatory reactions in the central nerve system and peripheral tissues. Thus, they may perform key functions in the pathophysiology of acute ischemic and hemorrhagic brain injury. The aim of this study was to evaluate the production of chemokines following acute brain injury (ABI) in humans. The correlations between the three main types of ABI(traumatic, ischemic and spontaneous hemorrhagic brain injury) and the plasma levels of three chemokines-CXCL8 (IL-8), CCL4 (MIP-1beta) and CCL5 (MIP-1beta)-were analyzed. METHODS: Enrolled in this study were 25 patients with isolated severe head trauma, 31 patients with spontaneous intracranial hemorrhage (SIH), and 34 patients with cerebral infarction. The AIS(abbreviated injury scale) was used to identify the isolated severe head trauma patients. The severities of several types of injury were assessed by ISS (injury severity score) in trauma, GCS (Glasgow coma scale) in SIH, and NIHSS(national institute of health stroke scale) in cerebral infarction. Blood samples from 9 healthy blood donors were analyzed as controls. Protein concentrations of CXCL8, CCL4, and CCL5 were measured by ELISA(enzyme-linked immunosorbent assay), and mRMA levels of XCL1(lymphotactin, Ltn), CCL5, CXCL10 (IP-10), CCL4, CCL3(MIP-alpha), CCL2 (MCP-1), CXCL8, and CCL1 (I-309) were evaluated using the RPA(multi-probe RNase protection assay) system in plasma and in peripheral blood mononuclear cells (PBMCs) from patients' venous blood obtained with 24 hours after injury. RESULTS: The expression patterns of XCL1, CCL5, CXCL8, CCL4, and CCL5 mRNA were similar in the three groups of ABI, without differences related to patterns of ABI or trauma severity. Concentrations of the three proteins CXCL8, CCL4, and CCL5 in plasma from all three ABI groups were higher than in the control group. The level of CXCL8 was significantly elevated in the TBI(traumatic brain injury) group (3.57+/-5.93 pg/ml, p<0.05), and this high level of IL-8 was significantly correlated with increased injury severity (high ISS and low GCS score) (p<0.05). The concentration of CCL4 was highest (29.82+/-17.94 pg/ml) in the ischemic brain injury group and was significantly higher than in the SIH group (p<0.05). The protein level of CCL4 was also elevated significantly with high ISS (p<0.05). The level of CCL5 was highest (7692+/-3603 pg/ml) in the SIH group and was significantly higher than in the TBI group (p<0.05). CONCLUSION: ABI resulted in a modest activation of CXCL8, CCL4 and CCL5, and the statistically significant correlations were found between the plasma levels of these chemokines and ABI. In addition, significant correlations were found between the plasma protein levels of CXCL8 and CCL4 and trauma severity in TBI group. Therefore, the continuous monitoring of various chemokine concentrations may provide a useful adjunct to assigning grouping and to gauging severity or prognosis in ABI.