Interleukin-6, MCP-1, IP-10, and MIG are sequentially expressed in cerebrospinal fluid after subarachnoid hemorrhage

Abstract

Background: Interleukin-6 (IL-6), an inflammatory cytokine, plays important roles in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). Chemokines are chemoattractant cytokines that regulate trafficking of monocytes/macrophages and lymphocytes to sites of inflammation. However, no studies have been reported regarding the temporal expression of these cytokines in CSF after SAH.

Findings: The concentrations of IL-6, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-inducible protein-10 (IP-10), and monokine induced by interferon-γ (MIG) in the CSF of ten patients with SAH were measured using ELISA kits over a period of 14 days. All aneurysms were located in the anterior circulation. CSF samples from patients with unruptured aneurysms were used as controls. The concentration of IL-6 significantly increased during the acute stage of the disease. The concentration of MCP-1 increased from days 1 to 5, peaking on day 3, and decreased thereafter. The concentrations of IP-10 and MIG progressively increased, peaked on day 5, and then gradually decreased. There were strong correlations between the maximum levels of IL-6 and MCP-1 and IP-10 and MIG on day 5. The maximum level of IL-6 was much higher in poor outcome patients than in good outcome patients.

Conclusions: The present investigation demonstrated that increases in IL-6 levels may induce the expression of MCP-1 in CSF after SAH, followed by increases in the expression of IP-10 and MIG. Dynamic changes in the levels of these cytokines may induce inflammation and may be closely associated with the development of delayed ischemic neurological deficits after SAH.

Keywords: IP-10; Interleukin-6; MCP-1; MIG; Subarachnoid hemorrhage.

Fig. 1

Dynamic changes in the levels of interleukin-6 (IL-6; a), monocyte chemoattractant protein-1 (MCP-1; b), interferon-γ-inducible protein-10 (IP-10; c), and monokine induced by interferon-γ (MIG; d) in the cerebrospinal fluid of ten patients with subarachnoid hemorrhage. Data are represented as box-and-whisker plots indicating the median, the upper and lower quartiles, and the largest and the lowest values. *p < 0.05 compared with control group via one-way ANOVA, followed by Fisher’s PLSD for multiple comparisons. The correlations between the peak concentration of IL-6 and that of MCP-1 (e) and the concentrations of IP-10 and MIG on day 5 (f), according to Pearson’s correlation coefficient. The open circle represents the data from the good outcome (good recovery (GR)) patients, while the closed circle represents the data from the poor outcome (moderate disability (MD) + vegetative state (VS)) patients. Peak concentrations of IL-6 (g) in the good outcome (GR) patients and poor outcome (MD + VS) patients. *p < 0.05 by Mann-Whitney U test