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Therapeutic benefits of interleukin 2 plus indomethacin
478 survival rate of the animals significantly, they had fewer positive blood cultures and significantly increased absolute neutrophil counts. Silver G. M., Gamelli R. L., Oreilly M. et al. (1990) The effect of interleukin-l-alpha on survival in a murine model of burn wound sepsis. Arch. Surg. 125,(7), 922-925.
Resuscitation of burns and burns plus smoke inhalation injuries Extravascular lung water content and p0, were measured in sheep with either a smoke inhalation injury or this injury combined with a deep burn covering 40 per cent of the body surface area. Compared with the findings following inhalation injury alone the added burn injury induced marked increases in extravascular lung water content and falls in p0,. In the sheep with both forms of injury resuscitation with Dextran 40 (compared with resuscitation with Ringers lactate) resulted in substantially lower accumulations of extravascular lung water and significantly improved ~0, levels. Schenk W. G., Aldridge S. C. and Farley P. C. (1990) Experimental inhalation injury with concomitant surface burn. Dextran resuscitation improves lung water and oxygenation. 1. Trauma 30,(7),
813-819.
Factors inducing postburn immune suppression Splenic lymphocyte proliferation, lymphocyte surface expression of activation antigens and peritoneal neutrophil oxidative burst activity were measured in mice 10 days following subcutaneous implantation of normal skin, burned skin cotton gauze or collagen sheet. All these implanted materials caused the suppression of both lymphocyte activation proliferation and neutrophil oxidative burst activity. Each material induced an intense local inflammatory reaction. Hansbrough J. F., Zapata-Sirvent R. and Hoyt D. (1990) Postburn immune suppression: An ir&mrnatory response to the burn wound.]. Trauma 30, (6), 671675.
Mesenteric blood flow, bacterial translocation, burn injury and smoke inhalation injury Mesenteric blood flow and bacterial translocation from the gut into the mesenteric lymph nodes, the liver, spleen, kidney and lung tissue was measured in sheep suffering from thermal injury alone, cotton smoke inhalation injury alone or combined burns and smoke inhalation injury. Burns alone reduced the mesenteric blood flow to 48 per cent of normal, it fell to 80 per cent of normal with smoke inhalation injury alone and 64 per cent with the combined injury. Burns as well as burns plus smoke injury caused higher levels of bacterial translocation than smoke injury alone. Bacterial translocation was minimal in uninjured animals. Morris S. E., Navartnam N. and Hemdon D. N. (1990) A comparison of effects of thermal injury and smoke inhalation on bacterial translocation. 1. Trauma 30, (6), 639-645.
Antibiotic gavage and gut bacterial translocation Bacterial translocation from the gut to the mesenteric lymph nodes was measured in rats with 30 per cent TBSA scalds that had been inoculated with Ps. ueruginesa and then given either saline or ampicillin gavage. The ampicillin administration was followed by an increase in caecal colony counts, an unchanged incidence of bacterial translocation and reductions in the numbers of organisms present in both the mesenteric lymph nodes and organs (i.e. there
Burns
(1990) Vol. 16/No._6
was caecal overgrowth with non-translocating bacteria). The reduced number of translocating organisms was not associated with an increase in mean survival tie. The degree of bacterial translocation did not appear to modify the mortality due to Ps. eemgino~a burn wound sepsis, which had previously been thought to enhance bacterial translocation. Jones W. G., Barber A. E.. Minei J. P. et al. (1990) Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis. 1. Trauma 30, (6), 737-740.
Burns,infection and small bowel permeabilities Bowel mass and bowel tissue composition and blood flow were measured in rats with scalds covering 30 per cent of the body surface area, half of which also had the bum wounds inoculated with Ps. aeruginosu. Compared with the findings in unburned rats and non-infected burned rats the burned infected animals showed a chronic loss of small bowel mass by 7 days after injury. Compositional alterations of the small bowels of burned and infected animals included protein wasting similar to, but occurring earlier than that seen with anorexia alone. There were also decreased DNA and RNA contents but unchanged tissue water contents. The intestinal atrophy was not due to persisting ischaemia because intestinal blood flows (measured with 51Cr labelled microspheres) were not abnormal. Jones W. G., Minei J. P., Barber A. E. et al. (1990) Additive effects of thermal injury and infection on the small bowel. .Sttr~cr~ 108, (I), 63-70.
Bum-induced early changes in small bowel permeability Small bowel permeability was tested in rats with severe scalds covering 20 per cent of the body surface area using polyethylene glycol3350 and horse radish peroxidase as permeability probes. Compared with the results in normal animals using these probes, within 6 h of injury there was an increase in the mucosal uptake and transmural permeability in all sections of the small bowel. The most dramatic change occurred in the ileum. The maximal increase in permeability occurred at 18h after injury, normal permeability had returned by 72 h after injury. This transient failure of the intestinal barrier may allow the absorption of potentially toxic macromolecules with possible direct toxic or immunological consequences. Carter E. A., Tompkins R. G., S&iffrin E. et al. (19sO) Cutaneous thermal injury alters macromolecular permeability of rat small intestine. Surgery 107, (3), 335-341.
Therapeutic benefits of interleukm t plus indomethacin Mice with and without scalds covering 25 per cent of the body surface area received recombinant human interleukin 2(rhIL-2) or saline or indomethacin alone or rhIL-2 plus indomethacin. Also some animals were made septicaemic. Mortality rates in animals which were burned and septic and not treated, in those receiving rhIL-2 alone and in those receiving indomethacin alone were between 62 and 75 per cent; whereas the mortality rate was reduced to only 38 per cent in mice receiving both rhIL-2 and indomethacin. Splenocytes from animals receiving this combination therapy had markedly improved responses to PHA and CON A. The combination therapy also significantly improved the animals own production of interleukin 2. Horgan P. G., Mannick J. A., Dubravec D. B. et al. (1990) Effect of low dosage recombinant interleukin-2 plus indomethacin on mortality after sepsis in a murine bum model. Br. I. Surg. 77, (4). 401-404.
Resuscitation of burns and burns plus smoke inhalation injuries Extravascular lung water content and p0, were measured in sheep with either a smoke inhalation injury or this injury combined with a deep burn covering 40 per cent of the body surface area. Compared with the findings following inhalation injury alone the added burn injury induced marked increases in extravascular lung water content and falls in p0,. In the sheep with both forms of injury resuscitation with Dextran 40 (compared with resuscitation with Ringers lactate) resulted in substantially lower accumulations of extravascular lung water and significantly improved ~0, levels. Schenk W. G., Aldridge S. C. and Farley P. C. (1990) Experimental inhalation injury with concomitant surface burn. Dextran resuscitation improves lung water and oxygenation. 1. Trauma 30,(7),
813-819.
Factors inducing postburn immune suppression Splenic lymphocyte proliferation, lymphocyte surface expression of activation antigens and peritoneal neutrophil oxidative burst activity were measured in mice 10 days following subcutaneous implantation of normal skin, burned skin cotton gauze or collagen sheet. All these implanted materials caused the suppression of both lymphocyte activation proliferation and neutrophil oxidative burst activity. Each material induced an intense local inflammatory reaction. Hansbrough J. F., Zapata-Sirvent R. and Hoyt D. (1990) Postburn immune suppression: An ir&mrnatory response to the burn wound.]. Trauma 30, (6), 671675.
Mesenteric blood flow, bacterial translocation, burn injury and smoke inhalation injury Mesenteric blood flow and bacterial translocation from the gut into the mesenteric lymph nodes, the liver, spleen, kidney and lung tissue was measured in sheep suffering from thermal injury alone, cotton smoke inhalation injury alone or combined burns and smoke inhalation injury. Burns alone reduced the mesenteric blood flow to 48 per cent of normal, it fell to 80 per cent of normal with smoke inhalation injury alone and 64 per cent with the combined injury. Burns as well as burns plus smoke injury caused higher levels of bacterial translocation than smoke injury alone. Bacterial translocation was minimal in uninjured animals. Morris S. E., Navartnam N. and Hemdon D. N. (1990) A comparison of effects of thermal injury and smoke inhalation on bacterial translocation. 1. Trauma 30, (6), 639-645.
Antibiotic gavage and gut bacterial translocation Bacterial translocation from the gut to the mesenteric lymph nodes was measured in rats with 30 per cent TBSA scalds that had been inoculated with Ps. ueruginesa and then given either saline or ampicillin gavage. The ampicillin administration was followed by an increase in caecal colony counts, an unchanged incidence of bacterial translocation and reductions in the numbers of organisms present in both the mesenteric lymph nodes and organs (i.e. there
Burns
(1990) Vol. 16/No._6
was caecal overgrowth with non-translocating bacteria). The reduced number of translocating organisms was not associated with an increase in mean survival tie. The degree of bacterial translocation did not appear to modify the mortality due to Ps. eemgino~a burn wound sepsis, which had previously been thought to enhance bacterial translocation. Jones W. G., Barber A. E.. Minei J. P. et al. (1990) Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis. 1. Trauma 30, (6), 737-740.
Burns,infection and small bowel permeabilities Bowel mass and bowel tissue composition and blood flow were measured in rats with scalds covering 30 per cent of the body surface area, half of which also had the bum wounds inoculated with Ps. aeruginosu. Compared with the findings in unburned rats and non-infected burned rats the burned infected animals showed a chronic loss of small bowel mass by 7 days after injury. Compositional alterations of the small bowels of burned and infected animals included protein wasting similar to, but occurring earlier than that seen with anorexia alone. There were also decreased DNA and RNA contents but unchanged tissue water contents. The intestinal atrophy was not due to persisting ischaemia because intestinal blood flows (measured with 51Cr labelled microspheres) were not abnormal. Jones W. G., Minei J. P., Barber A. E. et al. (1990) Additive effects of thermal injury and infection on the small bowel. .Sttr~cr~ 108, (I), 63-70.
Bum-induced early changes in small bowel permeability Small bowel permeability was tested in rats with severe scalds covering 20 per cent of the body surface area using polyethylene glycol3350 and horse radish peroxidase as permeability probes. Compared with the results in normal animals using these probes, within 6 h of injury there was an increase in the mucosal uptake and transmural permeability in all sections of the small bowel. The most dramatic change occurred in the ileum. The maximal increase in permeability occurred at 18h after injury, normal permeability had returned by 72 h after injury. This transient failure of the intestinal barrier may allow the absorption of potentially toxic macromolecules with possible direct toxic or immunological consequences. Carter E. A., Tompkins R. G., S&iffrin E. et al. (19sO) Cutaneous thermal injury alters macromolecular permeability of rat small intestine. Surgery 107, (3), 335-341.
Therapeutic benefits of interleukm t plus indomethacin Mice with and without scalds covering 25 per cent of the body surface area received recombinant human interleukin 2(rhIL-2) or saline or indomethacin alone or rhIL-2 plus indomethacin. Also some animals were made septicaemic. Mortality rates in animals which were burned and septic and not treated, in those receiving rhIL-2 alone and in those receiving indomethacin alone were between 62 and 75 per cent; whereas the mortality rate was reduced to only 38 per cent in mice receiving both rhIL-2 and indomethacin. Splenocytes from animals receiving this combination therapy had markedly improved responses to PHA and CON A. The combination therapy also significantly improved the animals own production of interleukin 2. Horgan P. G., Mannick J. A., Dubravec D. B. et al. (1990) Effect of low dosage recombinant interleukin-2 plus indomethacin on mortality after sepsis in a murine bum model. Br. I. Surg. 77, (4). 401-404.