title: Effects of extracellular pressure and alcohol on the microglial response to inflammatory stimulation.
abstract: BACKGROUND
  Traumatic brain injury induces a neuroinflammatory response frequently associated with increased intracranial pressure. The aim of this study was to investigate the effects of alcohol and increased extracellular pressure on murine BV-2 microglial proliferation and cytokine responses to lipopolysaccharide (LPS) stimulation.
  
  
  METHODS
  BV-2 cells were cultured under 0 or 30 mm Hg increased extracellular pressure without or with ethanol (100 mmol/L) or LPS (10 ng/mL) for 24 hours. Cell proliferation was assessed using MTS assay and secretion of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Increased pressure and LPS stimulation each promoted proliferation. Ethanol pretreatment blocked these effects. Basal TNF-α and IL-6 secretion was at the limits of delectability. Basal MCP-1 production was stimulated by pressure, which was blocked by ethanol. Even this low LPS dose stimulated microglial secretion of TNF-α, IL-6, and MCP-1. Pressure inhibited LPS-stimulated production of these proinflammatory cytokines, while ethanol pretreatment blocked LPS-stimulated cytokine production. The combination of pressure and ethanol further reduced TNF-α, IL-6, and MCP-1 secretion by LPS-stimulated microglial cells.
  
  
  CONCLUSIONS
  Alcohol's anti-inflammatory effects may contribute to the reduced mortality from traumatic brain injury that some have described in acutely intoxicated patients, while pressure down-regulation of inflammatory cytokine release could create a negative feedback that ameliorates inflammation in traumatic brain injury.
authors.affiliation: Department of Surgery, Michigan State University, Lansing, MI, USA.
authors.forename: Lakshmi S
authors.initials: LS
authors.lastname: Chaturvedi
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Marc D
authors.initials: MD
authors.lastname: Basson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D011312:Pressure / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol