Does uninjured skin release proinflammatory cytokines following trauma andhemorrhage?

Hypothesis: Uninjured skin contributes to the elevation in circulating leve l's of proinflammatory cytokines seen following severe injury. Design: Male C3H/HeN mice underwent trauma, trauma-hemorrhage and resuscita tion, or closed long-bone fracture. Serum, skin, and liver samples were har vested at designated times after experimental treatment. Main Outcome Measures: Levels of interleukin (IL) I beta, IL-6, and tumor n ecrosis 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 l iver and skin samples at 1, 2, 4, 8, and 24 hours from all 3 experimental g roups, and gene expression of the cytokines was determined. Results: Remote (nontraumatized) skin from trauma-hemorrhage animals releas ed significantly more IL-6 and TNF-alpha into culture supernatants at 1 and 24 hours and significantly more IL-1 beta at 1, 8, and 24 hours than did s kin from sham animals. Serum levels of all 3 cytokines were significantly e levated at 1 and 24 hours after trauma-hemorrhage relative to sham animals. Gene expression of all 3 cytokines was detected in skin and liver followin g trauma-hemorrhage. Furthermore,gene expression of all 3 cytokines was det ected in uninjured skin after soft tissue trauma and closed long-bone fract ure. Conclusions: Proinflammatory cytokine gene expression is up-regulated in un injured skin following trauma, trauma-hemorrhage, and long-bone fracture. T his increase in gene expression correlates with increased cytokine producti on by cultured skin as well as increased circulating cytokine levels. These results suggest that uninjured skin may also contribute to the rise in cir culating cytokine levels seen after injury.