Raised parenchymal interleukin-6 levels correlate with improved outcome after traumatic brain injury

Previous studies have suggested that an increased production of the pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) can influence patient outcome following a severe head injury. However, these studies have relied upon measurements of cytokine levels in CSF or serum, rather than the brain parenchyma itself. Recently, a method of intracranial microdialysis has been developed which permits the efficient recovery of macromolecules from the parenchyma. We have used this technique to investigate whether there is a correlation between patient outcome and parenchymally derived cytokines. Fourteen patients who were admitted to the Wessex Neurological Centre with severe head injury were selected for the study. This group of patients consisted of seven males and seven females with an age range of 21-77 years. Patients were treated according to standard protocols including emergency craniotomy where necessary. Microdialysis probes were implanted into the frontal region contralateral to the site of the primary injury. Approximately 200 mul of dialysate was recovered every 8-12 h, and the concentrations of IL-6, IL-1beta and nerve growth factor (NGF) were determined by commercial enzyme-linked immunosorbent assays. Patients were assessed initially using the Glasgow coma score, and survivors were assessed after 6 months using the Glasgow outcome scale. Significantly (P = 0.04) higher levels of IL-6 were found in patients who survived compared with those who died. Also, there was a significant correlation between peak IL-6 levels and Glasgow outcome scores (r(2) = 0.34, P = 0.03, n = 14). The levels of IL-1beta and NGF were similar in both groups of patients. From these data, we suggest that IL-6 is an endogenous neuroprotective cytokine produced in response to severe head trauma.