Search

Since the early 1970s, there have been reports that anesthesia and blood transfusions impair the body's immune function and increase the risks associated with surgery. The authors previously reported that both anesthesia and blood transfusion decreased the survival rate in rats with peritonitis (inflammation of the lining of the abdominal cavity), which was caused by Escherichia coli, a bacteria normally found in the intestinal tract. The current study was undertaken to determine if this decreased survival is due to changes in patients' responses to the endotoxin. Endotoxin is a poison contained in the walls of some microorganisms, particularly intestinal bacteria; when the bacteria die, endotoxin is released and broken down in the body. Using an animal model (rats), it was found that when blood transfusion or anesthesia was administered two days before endotoxin challenge, there was no change in mortality. However, when blood transfusion was given seven days prior to endotoxin challenge, the survival rate increased. In addition, some endotoxin-related changes in white blood cells did not occur, and blood levels of tumor necrosis factor (TNF) decreased. These results differ from previous findings, and suggest that, under certain circumstances, blood transfusions may depress immune function in a beneficial manner. In this animal model, the 81 percent decrease in the TNF level may have been responsible for improved survival; increases in TNF have been reported to be a major factor in endotoxic shock. Although blood transfusion may increase the risk of infection, it may also enable the body to respond to the endotoxic complications of those infections. (Consumer Summary produced by Reliance Medical Information, Inc.)

Injury elicits a response from all cells of the immune system in which cytokines and other metabolic products of activated leukocytes can act either beneficially to provide for enhanced host resistance or deleteriously to depress the function of remote organs and cause what has been termed systemic inflammation. These at times antithecal responses of leukocytes that appear to integrate postinjury changes in the neuroendocrine, immune, and coagulation systems have been implicated as principal causative factors in multiple systems organ failure. Numerous investigators have evaluated a variety of therapeutic agents to prevent and control infection by restoring leukocyte function, while others have evaluated antagonists and monoclonal antibodies as a means of controlling the exaggerated and persistent actions of leukocytes and cytokines caused by systemic inflammation. The redundancies of the cell populations and the cytokines and other metabolites produced by the cells predictably limit the effectiveness of any single agent and make clinical evaluation of such agents difficult.(Arch Surg. 1993;128:1260-1267)

• We studied the effects of granulocyte-macrophage colony-stimulating factor in burn patients. Serial measurements of granulocyte oxidative function were obtained in treated patients and in a group of controls matched for age and total burn size. The administration of granulocyte-macrophage colony-stimulating factor resulted in a 50% increase in mean leukocyte counts. Both groups showed significant baseline increases in granulocytic cytosolic oxidative function. Treated patients showed normal stimulated cytosolic oxidative function, which was significantly depressed compared with that of untreated patients. Myeloper-oxidase activity was increased in treated patients during the first postburn week but then declined to normal levels. Untreated patients had a significant increase in myeloperoxidase activity for the first 3 weeks following injury. Untreated patients exhibited a significant decrease in superoxide activity during the second 3 weeks following injury. Treated patients demonstrated normal superoxide activity.(Arch Surg. 1991; 126:74-79)

The interrelationship among burn injury, zinc metabolism, and circulating T-lymphocyte distribution was studied using a rat model. Sixty Sprague-Dawley male rats were fed a zinc-deficient (<0.5 ppm) semipurified diet and given daily subcutaneous injections of 1 mg Zn/kg body wt for 14 days. On Day 15, 24 of the rats were subjected to a full-thickness dorsal scald injury of 30% of the total body surface. Half of the burned rats were continued on the zinc supplementation (BS) while the other half were maintained on the zinc-deficient (BD) regimen by injecting physiological saline. Feces and urine were collected for 10 days postburn and subsequently analyzed for zinc content. On Day 10 postburn all the rats were sacrificed. Zinc bound to cytosol proteins in hepatic and intestinal mucosal tissue was determined by gel column chromatography procedures and T-lymphocyte subset distributions were determined by flow cytometry. No significant difference (P< 0.05) in total endogenous zinc excretion was seen among treatment groups. A dramatic increase was seen in zinc bound to a 12,000 mol wt protein in hepatic tissue from the BS group only. The only significant (P< 0.05) change in T-lymphocyte populations was an increase in T-suppressor cells in the BD group.

• The effects of prophylactic administration of intravenous IgG on immune-cell phenotype and function in burn patients were compared with those of patients receiving standard therapy. Intravenous IgG infusions were given twice weekly for three weeks postburn or until wound closure. Intravenous IgG had no effect on the proportion of total T-lymphocytes, T-helper lymphocytes, or T-suppressor lymphocytes, but the proportion of B-lymphocytes decreased 40% in treated patient samples. Lymphocytes from treated patients incorporated less thymidine when stimulated with concanavalin A or pokeweed mitogen, but not with phytohemagglutinin. The amount of IgM secreted by pokeweed mitogen-stimulated cultures from treated patients increased by 24%, while the amount of IgG remained constant. The changes in β-lymphocyte number and functional response may have been induced by the increased serum IgG levels in the intravenous IgG—treated patients.(Arch Surg 1988;123:1379-1382)

• Increased infection rates in burned patients may result from a disproportionate increase in the suppressor subpopulations. Measurement of lymphocyte subpopulations is difficult in burned patients because gradient-purified cells are contaminated by nonlymphoid cells. The accuracy of flow cytometric subpopulation analysis was improved by restricting (gating) the analysis to cells with light-scatter intensity typical of lymphocytes. Blood was obtained 48 hours after burn from rats receiving no burns, 30% scald burns, or burns seeded with Pseudomonas aeruginosa to induce infection. Subpopulations were identified by monoclonal antibodies to T-lymphocyte antigens. Gating increased the values obtained for most subpopulations, but the relative differences between groups were unchanged. Burned and infected animals, but not animals burned only, had a decreased ratio of helper to suppressor lymphocytes (HSR) relative to control. A decreased HSR correlated with sepsis, but not with infection susceptibility. This suggests that a decrease in HSR may be a result of infection rather than a cause of susceptibility to infection.(Arch Surg 1987;122:216-220)