Disruption of gut barrier function and cytokine responses after severe surgical stress-mechanism and treatment

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Experimenr IEffects of growth hormone (GH) and insulin-like growth factor I (IGF-I) administration on burn induced gut derived sepsis was evaluated. BALB/c mice (n=50) were treated subcutaneously with 4.8mg/kg/day of GH,24mg/kg/day of IGF-I or placebo twice a day for 4 days. Then they were gavaged with 10^<10>E.coli and subjected to 20% full sickness flame burn. All mice received allogeneic blood transfusion 5 days before burn to induce mild immunosuppression. Thirty mice were observed for survival and twenty mice were sacrificed at 20 hours post burn. GH and IGF-I administration reduced the incidence of translocation to MLN and other organs 20 hours post burn and significantly improved survival. We conclude that GH and IGF-I may be useful during critical illness.Experiment IIThe previous investigation revealed that bacterial translocation is highly associated with mortality after burn injury. To further clarify the mechanism of bacterial translocation related organ dysfunction and sub … More sequent death, we investigated the relation between the degree bacterial translocation and neutrophil accumulation in the liver.Blood transfused Balb/c mice were treated with oral 200mg/kg/day enisoprost (PGEl analog) or saline for three days and then they were gavaged with 10^<10 14>C E.coli and 20% full sickness flame burn was inflicted. According to our previous investigation, these mice have a mortality rate of approximately 80% and enisoprost improved the mortality to up to 30%. Animals were sacrificed 24 hour post burn and mesenteric lymph node (MLN), Liver, and spleen were harvested. Bacterial translocation were determined by both radionuclide count (dpm) and viable colony count in the MLN and Liver. Leukocyte accumulation was evaluated by the measurement of myeloperoxidase (MPO) in the liver. Consistent to previous work, enisoprost significantly reduced the translocation. MPO in the liver was significantly greater in the control group compared to enisoprost group. There was a significant correlation between MPO and the degree of bacterial translocation (p<0.05). It can concluded that bacterial translocation enhanced neutrophil accumulation in the liver which may be the cause of organ injury after burn injury.Experiment IIIUsing the same model as experiment II,splenic macrophages were separated and cultured for 24 hours with and without 10mcg/ml of LPS.TNF,IL-1 IL-6 and PGE2 in the cell culture supernatants were measured. LPS stimulated macrophage production of IL-1, IL-6 and PGE2 were significantly greater in enisoprost treated animals. It is likely that prior lack of in vivo maximal stimulation of macrophages in the enisoprost treated animals can produce greater amounts of cytokines when further stimulated with LPS in vitro. Less