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.

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)–⍺, interleukin (IL)–6, and monocyte chemotactic protein (MCP)–1 by enzyme-linked immunosorbent assay.

Increased pressure and LPS stimulation each promoted proliferation. Ethanol pretreatment blocked these effects. Basal TNF-⍺ 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-⍺, 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-⍺, IL-6, and MCP-1 secretion by LPS-stimulated microglial cells.

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.