Does uninjured skin release proinflammatory cytokines following trauma and hemorrhage?
OBJECTIVE
Uninjured skin contributes to the elevation in circulating levels of proinflammatory cytokines seen following severe injury.


METHODS
Male C3H/HeN mice underwent trauma, trauma-hemorrhage and resuscitation, or closed long-bone fracture. Serum, skin, and liver samples were harvested at designated times after experimental treatment.


METHODS
Levels of interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were determined in serum and skin cultures at 1, 8, and 24 hours after trauma-hemorrhage. The RNA was isolated from liver and skin samples at 1, 2, 4, 8, and 24 hours from all 3 experimental groups, and gene expression of the cytokines was determined.


RESULTS
Remote (nontraumatized) skin from trauma-hemorrhage animals released significantly more IL-6 and TNF-alpha into culture supernatants at 1 and 24 hours and significantly more IL-1beta at 1, 8, and 24 hours than did skin from sham animals. Serum levels of all 3 cytokines were significantly elevated at 1 and 24 hours after trauma-hemorrhage relative to sham animals. Gene expression of all 3 cytokines was detected in skin and liver following trauma-hemorrhage. Furthermore, gene expression of all 3 cytokines was detected in uninjured skin after soft tissue trauma and closed long-bone fracture.


CONCLUSIONS
Proinflammatory cytokine gene expression is up-regulated in uninjured skin following trauma, trauma-hemorrhage, and long-bone fracture. This increase in gene expression correlates with increased cytokine production by cultured skin as well as increased circulating cytokine levels. These results suggest that uninjured skin may also contribute to the rise in circulating cytokine levels seen after injury.
Catania
R A
RA
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
Schwacha
M G
MG
Cioffi
W G
WG
Bland
K I
KI
Chaudry
I H
IH
D000818:Animals; D015870:Gene Expression; D006470:Hemorrhage / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012867:Skin / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014947:Wounds and Injuries / Q000276:immunology*
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha