Prostaglandin and tumor necrosis factor levels in early wound inflammatory fluid: Effects of parenteral omega-3 and omega-6 fatty acid administration

Abstract

Monokines are important mediators of wound healing. Specifically, the proportions of proinflammatory (tumor necrosis factor and PGE 2) and antiinflammatory (PGF 2α) monokines may modulate its early phases. Using a polyvinyl alcohol sponge model of rat wounding, the authors determined the temporal changes in the levels of monokines in wound inflammatory fluid, and examined whether dietary manipulation for 6 days with the precursors (ω6 fatty acids) and inhibitors (fish oil ω3 fatty acids) of the prostaglandin-2 series influenced monokine composition of wound fluid. For 3 days before the wounding, adult rats received isocaloric, isovolemic, and isonitrogenous total parenteral nutrition (TPN), in which lipids supplied either 35% (Intralipid [IL] or fish oil emulsion [FO]) or 8% (minimal essential fatty acid; EFA) of the total calories. Control rats received isocaloric enteral chow. The controls were studied at 24, 48, 72, and 96 hours, and the experimentals at 72 hours after wounding. Cell counts were performed, and cell-free fluid was analyzed for PGE 2, PGF 2α, and TNF. In control rats, the total WBC count was highest at 24 to 48 hours, and decreased significantly by 96 hours. The percentage of mononuclear cells progressively increased throughout the 96 hours, and the total mononuclear cell count peaked at 72 hours. The TNF and prostaglandin levels were highest at 24 hours; these decreased rapidly by 72 hours. At all time-points, the levels of PGE 2 remained higher than those of PGF 2α. Seventy-two hours postwounding, the different intravenous lipid preparations did not significantly after the WBC count, mononuclear cell count, or prostaglandin levels when compared with the 72-hour control, or with each other. However, TNF levels were significantly higher in the EFA low-fat group than in the high-fat IL or FO groups. This study confirms TNF's early role in wound healing, and provides previously undescribed evidence suggesting that PGE 2 and PGF 2α also help initiate the early inflammatory phase of wound healing. That all monokines peaked before the mononuclear cell peak suggests a functionally diverse, tightly regulated monocyte population differing in degree of activation over time. The lack of a temporal inversion of the PGE 2:PGF 2α ratio differs from previous studies that suggest that this ratio inverts as the inflammatory phase wanes. Interestingly, neither of the high-fat TPN preparations (IL or FO) resulted in significantly different monokine levels. However, the low-fat TPN preparation (EFA) did result in significantly increased wound TNF levels, which suggests that low quantities of exogenous fat may be more important than the type of fat for optimal wound healing.