Production of tumor necrosis factor-alpha and interleukin-1beta by human cerebral microvascular endothelium after percussive trauma.
Intracerebral cytokine production is thought to be partially responsible for the brain edema and increased leukocyte adhesion seen after head injury by both a direct effect on vascular permeability and by causing leukocyte activation. Cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 are elevated after traumatic brain injury. The cerebral endothelium has not been investigated as a de novo source of cytokines after injury. We have found that conditioned media from cultured human cerebral microvascular endothelium (HCME) subjected to percussion trauma increases neutrophil chemotaxis. To test the hypothesis that percussive trauma increases the production of TNF-alpha and IL-1beta by HCME, serial supernatant samples from passage 2 HCME were collected for 24 hours and analyzed for TNF-alpha and IL-1beta concentration by enzyme-linked immunosorbent assay after trauma. HCME subjected to percussion injury secreted significantly more TNF-alpha at 8 and 24 hours and significantly more IL-1beta at 4 and 24 hours compared with uninjured controls (p < 0.05, Student's t test). These data suggest that HCME production of inflammatory cytokines occurs after traumatic brain injury independent of systemic influences. In situ cytokine production by HCME after percussion trauma may mediate the increased cerebral leukocyte accumulation and cerebrovascular dysfunction observed after focal brain injury.
Gourin
C G
CG
Department of Surgery, College of Medicine, University of Vermont, Burlington, USA.
Shackford
S R
SR
D001930:Brain Injuries / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D009504:Neutrophils / Q000502:physiology; D009622:Noise; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha