In situ detection of intracerebral cytokine expression after human brain contusion

The study was undertaken to analyze intracerebral expression of pro- and anti-inflammatory cytokines after traumatic brain injury (TBI) in man in order to compare the findings with previous experimental data regarding the pathogenesis of secondary brain injury. Contused brain tissue biopsies were obtained from 12 consecutive patients undergoing surgery for brain contusions 3 h to 5 days after trauma. Cytokine expression was analyzed by in situ hybridization and immunohistochemistry. In patients undergoing surgery less than 24 h after trauma, strong expression of both the pro-inflammatory cytokines interleukin (IL)-1-beta, IL-6 and interferon (IFN)-gamma and the anti-inflammatory cytokine IL-4 was detected. In patients undergoing surgery between 3 and 5 days after trauma, IL-4 expression was significantly lower (P < 0.05) compared to the patients operated early. IL-1-beta and IFN-gamma expression remained strong in comparison to IL-6 and IL-4 expression (P < 0.05). Immunohistochemistry for IL-1-beta confirmed that the protein was produced with a temporal and regional pattern that corresponded to in situ hybridization results. The study provides in situ data on intracerebral cytokine expression after contusion in the clinical setting. Strong intracerebral cytokine expression occurs in the perilesional zone both in the early and the delayed phase after traumatic brain injury in humans. The temporal regulation of pro- and anti-inflammatory cytokines differs which reveals different therapeutic windows for pharmacological intervention.