Novel potentiation of interleukin 1alpha production in endotoxin-stimulated IC-21 cells by ambient pressure augmentation.
BACKGROUND
We hypothesized that increased ambient pressure would increase the production of interleukin 1alpha by endotoxin-stimulated macrophages, based on the clinical observation that patients with "pus under pressure" demonstrate systemic toxic effects (a priori hypothesis).


METHODS
In vitro experiment in the laboratory.


METHODS
A murine macrophage line, IC-21 cells, was seeded into 6-well plates, 25 x 10(4) 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 1alpha 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.


METHODS
The IC-21 production of interleukin 1alpha.


RESULTS
Interleukin 1alpha production at 2, 4, 8, and 12 hours (mean [+/-SD] picograms per 10(6) 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-1alpha 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-1alpha 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."
Sawyer
M D
MD
Department of Surgery, Yale University School of Medicine, New Haven, Conn 06510, USA.
van Raaij
T
T
Cross
J
J
Sumpio
B E
BE
D000818:Animals; D002461:Cell Line, Transformed; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011312:Pressure
D007375:Interleukin-1; D008070:Lipopolysaccharides