The relationship between IL-6, ET-1 and cerebral vasospasm, in experimental rabbit subarachnoid hemorrhage

In subarachnoid hemorrhage (SAH), occurrence of cerebral vasospasm (CVS) mediated by endothelin (ET)-1 might be a result of a compartmental inflammatory response with interleukin (IL)-6 release. We aim to investigate the relationship between ET-1 and IL-6 in association of CVS.

A total of 24 New Zealand white rabbits where randomly allocated into 3 groups: SAH (N.=10), IL-6 (N.=10), and sham (N.=4). SAH was induced by a closed cranium extracranial-intracranial shunt model. In the IL-6 group, IL-6 was injected into the cisterna magna. CVS of the basilar artery was assessed by digital subtraction angiography. IL-6 and ET-1 concentrations were measured using enzyme-linked immunosorbent assay. Neuronal damage was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling.

A significant increase between baseline (day 0) and follow-up (day 3) was found in CSF IL-6 levels of animals in the SAH and IL-6 group. There was a statistically significant correlation between IL-6 and ET-1 levels in the CSF (Pearson's r=0.454, P=0.003). CVS at day 3 was more pronounced in the SAH than in the IL-6 group: 26.0 ±7.2 % and 16.7 ±5.0 % respectively. TUNEL positive apoptotic neurons in the hippocampal formation were present in the SAH group and in a lesser degree in the IL-6 group.

The results indicate that IL-6 triggered CVS after SAH is ET-1 dependent. IL-6 may be a target for new therapeutic approaches.