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Cytokine-mediated inflammatory cell recruitment into the brain is a critical step in the response to diverse insults, including infection, trauma, and stroke. Hence, continous intra-cerebroventricular infusion of interleukin (IL)-1beta leads to an impressive cell invasion into the cerebrospinal fluid, as well as the brain parenchyma. Neither tumor necrosis factor-alpha nor IL-6 induced any significant cell invasion at all. However, the diverse immune cells (granulocytes, monocytes/macrophages) showed a different time course of invasion. Moreover, there was an association between the number of infiltrating immune cells and the infused IL-1 concentration. By analyzing intra-brain immune events, we demonstrated a time- and dose-dependent induction of intercellular adhesion molecule (ICAM)-1, whereas there were no differences for P-selectin, vascular cell adhesion molecule (VCAM)-1, and monocyte-chemotractant protein (MCP)-1, comparing vehicle and IL-1-infused animals. In conclusion, we assume IL-1beta to be a key cytokine for the granulocyte and monocyte recruitment into the central nervous system after various insults. However, granulocytes anticipate monocyte invasion.

To elucidate the role of cytokines in brain repair processes and in local inflammation after neurosurgical procedures, cerebrospinal fluid (CSF) samples from 8 patients with intra-axial tumours and 8 patients with extra-axial tumours were analysed for interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1 ra), IL-6, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha at the beginning and after surgery. Levels of IL-6 and IL-8 increased dramatically in all patients just hours after surgery and fell during subsequent days. IL-1 beta was found only in low amounts in the CSF of both patient groups. Other cytokines demonstrated different courses. In patients with intra-axial tumours IL-1 ra peaked two to four hours after surgery with a subsequent decrease. In patients with extra-axial tumours there was a continuous low-level IL-1 ra release into the CSF without a peak. TNF-alpha was not present in detectable levels in the CSF after surgery for extra-axial tumours but was found to peak two to four hours after surgery for intra-axial tumours. IL-10 was detected in the CSF of both patient groups, but a higher peak was seen after surgery for extra-axial tumours. These results suggest different requirements for the cytokine response and an involvement of different cell types in cytokine release. However, the analysis of the CSF from both patient groups showed no differences in cell counts and populations, with a mild pleocytosis being present in both patient groups after surgery. Therefore, we conclude that after surgery for extra-axial tumours cytokines were predominately produced by non-immune cells stimulated through hypoxia or mechanical irritation. After surgery for intra-axial tumours with a significant brain injury immune cells-activated by necrotic material-seen to be involved in the process of cytokine synthesis. In these cases an additional IL-1ra and TNF-alpha peak was found and these cytokines may be markers for cerebral injury.