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Immunodepression caused by burns and cyclosporin A
339
Abstarcts lethal COHb levels and in 14 of 20 victims with sublethal COHb levels, Thus cyanide is a major contributor, and in some cases the primary measured toxicant, in many patients suffering from smoke inhalation injury. Silvermann S. H., Purdue G. F., Hunt J. L. et al. (1988) Cyanide toxicity in burned patients. J. Trauma 28, (2), 171-176.
ANIMAL STUDIES lmmunodepression and cyclosporin A
caused
by burns
Modulation
A study in rats confirmed the hypothesis that burns and cyclosporin A cause potent cell-mediated immune suppression by similar mechanisms. The experimental technique involved the use of antisera produced across a full allogeneic barrier/major histocompatibility complex and allogeneic target splenocytes from rats with 40 per cent full skin thickness burns or lymphocytes from long-term cyclosporin-treated rats. The decreased reactivity induced by thermal injury was transferable to pooled normal splenocytes or blood lymphocytes by preincubation with burn plasma, which was confirmed by a cellular enzyme-linked immunoabsorbent assay. Hewitt C. W., Black K. S., Gonzalez G. A. et al. (1987) Decreased reactivity of allosera against target lymphocytes obtained following thermal injury or long term cycClin. Immunol. Immunopathol. 45, losporin treatment. (3), 385-404.
Nutritional
benefits
hypersensitivity) nor non-specific immunity (Staph. aureus skin abscess). In contrast in the protein-deficient rats Biostim augmented both the cell-mediated and the non-specific immune suppression but did not affect the humoral immunity. Christou N. V., Zakaluzny I., Marshall J. C. et al. (1988) The effect of the immunomodulator RU41740 (Biostim) on the specific and non-specific immunosuppression induced by thermal injury or protein deprivation. Arch. Surg. 123, (2). 207-211.
of fish oil
The nutritional support of guinea-pigs with deep flame burns covering 30 per cent of the body surface area contained 5,15,30 or 50 per cent of non-protein energy as fish oil. After 14 days enteral feeding via a gastrostomy tube there were no significant differences in resting metabolic expenditure or the serum levels of albumin or transferrin. Body weight loss was significantly greater and the carcass and liver weights were significantly smaller when the two higher levels of fish oil were given compared with use of the two lower levels, suggesting that the lower inputs of fish oil were more nutritionally beneficial. Cell-mediated immunity, macrophage bactericidal and opsonic indices were not different between the four groups. The higher levels of fish oil did not adversely affect immunity, possibly because it contains high concentrations of w3 fatty acids which are not precursors of immunosuppressive prostaglandin E2. Trocki O., Heyd T. J., Waymack J. P. et al. (1987) Effects of fish oil on postburn metabolism and immunity. J. Parent. Entr. Nutr. 11, (6), 521-528.
lmmunomodulation of specific non-specific immunity
and
The effects of Biostim (an immunomodulator) were tested in rats with deep burns covering 30 per cent of the body surface area and in protein-deficient rats (2 per cent protein diet for 8 weeks). The results showed that Biostim partially overcame the suppression in humoral immunity following bums (determined as antitetanus toxoid antibody production), but not the cell-mediated (delayed type
of leucocyte
activation
Rabbits with burns covering 25 per cent of the body surface area showed an early enhanced polymorphonuclear leucocyte generating capacity for superoxide radical, for the arachidonic acid lipooxygenase metabolite leukotriene B4 and for platelet activating factor acether. All these changes could be greatly reduced by the i.v. injection of a mixture of flavenoids and other polyphenols extracted from Ginkgo biloba. Lavaud P., Mathieu J., Bienvenu P. et al. (1988) Modulation of leucocyte activation in the early phase of the rabbit burn injury. Burns 14, (I), 15-20.
Differing
lymphocyte
subpopulations
The changes in the various types of lymphocytes found in blood, spleen and lymph nodes were measured in rats with full skin thickness burns covering 30 per cent of the body surface alone or with similar burn wounds that had been contaminated with Ps.aerufinosa. Flow cvtometrv ” 48 h after injury showed that: I, Helper lymphocytes were selectively depleted from the circultion by burns plus infection but not by burns alone, which caused the ratio of helper to suppressor cells in burns plus infection to decrease significantly compared with unburned controls. 2. Both lymph node helper and suppressor cells were decreased in burns plus infection animals and the helper/ suppressor cell ratio was unchanged. There was a selective reduction in suppressor cells in burns only lymph nodes, which increased the helper/suppressor cell ratio compared with unburned controls. 3. Spleen subpopulations were unchanged for both burns and burns plus infection groups. Burleson D. G., Mason A. D. and Pruitt B. A. (1988) Lymphoid subpopulation changes after thermal injury and thermal injury with infection in an experimental model. Ann. Surg. 207. (2), 208-212.
Smoke-induced chanaes
cardiopulmonary
Instrumented awake goats spontaneously inhaled wood smoke for a mean exposure time of 33 min, inducing peak COHb levels of 37 per cent. All animals survived for at least 24 hand showed only transient abnormalities in lung fluid balance and gas exchange. There was no measured change in lung mechanics or plasma levels of TXB2 or 6 keto PGF,,. However the extravascular lung water at 24 h was increased 33 per cent suggesting the presence of some airway oedema and retained secretions.
Abstarcts lethal COHb levels and in 14 of 20 victims with sublethal COHb levels, Thus cyanide is a major contributor, and in some cases the primary measured toxicant, in many patients suffering from smoke inhalation injury. Silvermann S. H., Purdue G. F., Hunt J. L. et al. (1988) Cyanide toxicity in burned patients. J. Trauma 28, (2), 171-176.
ANIMAL STUDIES lmmunodepression and cyclosporin A
caused
by burns
Modulation
A study in rats confirmed the hypothesis that burns and cyclosporin A cause potent cell-mediated immune suppression by similar mechanisms. The experimental technique involved the use of antisera produced across a full allogeneic barrier/major histocompatibility complex and allogeneic target splenocytes from rats with 40 per cent full skin thickness burns or lymphocytes from long-term cyclosporin-treated rats. The decreased reactivity induced by thermal injury was transferable to pooled normal splenocytes or blood lymphocytes by preincubation with burn plasma, which was confirmed by a cellular enzyme-linked immunoabsorbent assay. Hewitt C. W., Black K. S., Gonzalez G. A. et al. (1987) Decreased reactivity of allosera against target lymphocytes obtained following thermal injury or long term cycClin. Immunol. Immunopathol. 45, losporin treatment. (3), 385-404.
Nutritional
benefits
hypersensitivity) nor non-specific immunity (Staph. aureus skin abscess). In contrast in the protein-deficient rats Biostim augmented both the cell-mediated and the non-specific immune suppression but did not affect the humoral immunity. Christou N. V., Zakaluzny I., Marshall J. C. et al. (1988) The effect of the immunomodulator RU41740 (Biostim) on the specific and non-specific immunosuppression induced by thermal injury or protein deprivation. Arch. Surg. 123, (2). 207-211.
of fish oil
The nutritional support of guinea-pigs with deep flame burns covering 30 per cent of the body surface area contained 5,15,30 or 50 per cent of non-protein energy as fish oil. After 14 days enteral feeding via a gastrostomy tube there were no significant differences in resting metabolic expenditure or the serum levels of albumin or transferrin. Body weight loss was significantly greater and the carcass and liver weights were significantly smaller when the two higher levels of fish oil were given compared with use of the two lower levels, suggesting that the lower inputs of fish oil were more nutritionally beneficial. Cell-mediated immunity, macrophage bactericidal and opsonic indices were not different between the four groups. The higher levels of fish oil did not adversely affect immunity, possibly because it contains high concentrations of w3 fatty acids which are not precursors of immunosuppressive prostaglandin E2. Trocki O., Heyd T. J., Waymack J. P. et al. (1987) Effects of fish oil on postburn metabolism and immunity. J. Parent. Entr. Nutr. 11, (6), 521-528.
lmmunomodulation of specific non-specific immunity
and
The effects of Biostim (an immunomodulator) were tested in rats with deep burns covering 30 per cent of the body surface area and in protein-deficient rats (2 per cent protein diet for 8 weeks). The results showed that Biostim partially overcame the suppression in humoral immunity following bums (determined as antitetanus toxoid antibody production), but not the cell-mediated (delayed type
of leucocyte
activation
Rabbits with burns covering 25 per cent of the body surface area showed an early enhanced polymorphonuclear leucocyte generating capacity for superoxide radical, for the arachidonic acid lipooxygenase metabolite leukotriene B4 and for platelet activating factor acether. All these changes could be greatly reduced by the i.v. injection of a mixture of flavenoids and other polyphenols extracted from Ginkgo biloba. Lavaud P., Mathieu J., Bienvenu P. et al. (1988) Modulation of leucocyte activation in the early phase of the rabbit burn injury. Burns 14, (I), 15-20.
Differing
lymphocyte
subpopulations
The changes in the various types of lymphocytes found in blood, spleen and lymph nodes were measured in rats with full skin thickness burns covering 30 per cent of the body surface alone or with similar burn wounds that had been contaminated with Ps.aerufinosa. Flow cvtometrv ” 48 h after injury showed that: I, Helper lymphocytes were selectively depleted from the circultion by burns plus infection but not by burns alone, which caused the ratio of helper to suppressor cells in burns plus infection to decrease significantly compared with unburned controls. 2. Both lymph node helper and suppressor cells were decreased in burns plus infection animals and the helper/ suppressor cell ratio was unchanged. There was a selective reduction in suppressor cells in burns only lymph nodes, which increased the helper/suppressor cell ratio compared with unburned controls. 3. Spleen subpopulations were unchanged for both burns and burns plus infection groups. Burleson D. G., Mason A. D. and Pruitt B. A. (1988) Lymphoid subpopulation changes after thermal injury and thermal injury with infection in an experimental model. Ann. Surg. 207. (2), 208-212.
Smoke-induced chanaes
cardiopulmonary
Instrumented awake goats spontaneously inhaled wood smoke for a mean exposure time of 33 min, inducing peak COHb levels of 37 per cent. All animals survived for at least 24 hand showed only transient abnormalities in lung fluid balance and gas exchange. There was no measured change in lung mechanics or plasma levels of TXB2 or 6 keto PGF,,. However the extravascular lung water at 24 h was increased 33 per cent suggesting the presence of some airway oedema and retained secretions.