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Novel Potentiation of Interleukin 1 Production in Endotoxin-Stimulated IC-21 Cells by Ambient Pressure Augmentation

Mark D. Sawyer, MD; Tom van Raaij; John Cross; Bauer E. Sumpio, MD, PhD

Arch Surg. 1998;133:438-441.

Background  We hypothesized that increased ambient pressure would increase the production of interleukin 1 by endotoxin-stimulated macrophages, based on the clinical observation that patients with "pus under pressure" demonstrate systemic toxic effects (a priori hypothesis).

Design and Setting  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 1 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 Hg and LPS, 500 ng/mL.

Main Outcome Measures  The IC-21 production of interleukin 1.

Results  Interleukin 1 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-1 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-1 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 data support the hypothesis that pressure may be a novel potentiator of the macrophage proinflammatory cytokine response to endotoxin. This provides a possible explanation for the phenomenon of systemic illness seen with "pus under pressure."

From the Department of Surgery, Yale University School of Medicine, New Haven, Conn.