Novel potentiation of interleukin 1α production in endotoxin-stimulated IC-21 cells by ambient pressure augmentation

Background: We hypothesized that increased ambient pressure would increase the production of interleukin 1α by endotoxin stimulated macrophages, based on the clinical observation that patients with 'pus under pressure' demonstrate systemic toxic effects (a priori hypothesis). Design and Settings: In vitro experiment in the laboratory. Interventions: A murine macrophage line, IC-21 cells, was seeded into 6-well plates, 25x10⁴ cells per well. Cells were incubated under atmospheric (ATM) or increased (ATM+60 mm Hg) ambient pressure (AP) in the presence or absence of endotoxin (lipopolysaccharide [LPS]). The IC-21 production of interleukin 1α was determined at 2, 4, 8, and 12 hours. Four groups were examined: group 1: AP ATM, no LPS group 2: AP ATM+60 mm Hg, no LPS; group 3: AP ATM and LPS, 500 ng/mL; and group 4: AP ATM+60 mm ligand LPS, 500 ng/mL. Main Outcome Measures: The IC-21 production of interleukin 1α. Results: Interleukin 1α production at 2, 4, 8, and 12 hours (mean [±SD] picograms per 10⁶ cells) was as follows: group 1: 3.0 (±5.9), 8.1 (±10.3), 50.5 (±51.1) and 6.1 (±4.1), respectively, group 2: 228.7 (±110.2), 141.0 (±141.8), 112.5 (±98.5), and 118.2 (±79.8), respectively; group 3: 37.2 (±13.3), 191.5 (±86.5), 627.3 (±184.3), and 600.7 (±67.1), respectively; and group 4: 601.2 (±49.9), 1050.9 (±190.6), 2684.2 (±562.2), and 3144.7 (±388.4), respectively. The production of IL-1α by group 3 was significantly greater (P<.04, unpaired Student t test) at 4, 8, and 12 hours than that by groups 1 or 2. LIkewise, the production of IL-1α by group 4 was significantly greater (P<.001, unpaired Student t test) at all time points than that by groups 1, 2, or 3. Conclusions: Our date support the hypothesis that pressure may be a novel potentiator of the macrophage pro-inflammatory cytokine response to endotoxin. This provides a possible explanation for the phenomenon of systemic illness seen with 'pus under pressure'.