Cora K. Ogle

To determine any potential benefit of feeding increased amounts of protein to hypermetbolic burned patients, 18 children with burns averaging 60% total surface area were randomized into two matched groups and studied serially for at least six weeks: the first group was given a normal diet with a balanced nutritional supplement, and the second group was supplemented with milk whey protein. The normal protein group received 87.1% of their desired caloric intake with 16.5% of calories from protein compared to 77.7% of desired caloric intake with 23.0% of calories from protein for the high protein group. Despite a higher caloric intake, the normal protein group had a worse opsonic index compared to the high protein group (0.42 +/- 0.04 vs. 0.62 +/- 0.05, p < 0.0007), lower levels of C3 (1371 +/- 55 vs. 1585 +/- 64 micrograms/ml, p < 0.01), lower levels of IgG (805 +/- 52 vs. 975 +/- 56 micrograms/ml, p < 0.03), lower levels of transferrin (200 +/- 10 vs. 283 +/- 18 mg/dl, p < 0.0001), lower levels of total serum protein (5.5 +/- 0.1 vs. 6.3 +/- 0.2 g/dl, p < 0.005), more bacteremic days (11% vs. 8%, p < 0.005) and worse survival (5/9--56% vs. 9/9--100%, p < 0.03). Patients receiving the high protein diet had significantly higher plasma levels of valine, lysine, threonine, leucine, aginine, isoleucine, proline, serine, asparagine, tryptophane, and tyrosine. Asparagine levels were significantly (p < 0.01) associated with better neutrophil function and opsonic index. Except for phenylalanine, significant associations were found for serum levels of each of the amino acids with concentrations of one or more serum proteins. These studies provide evidence that many immunologic functions are dependent upon optimal availability of specific amino acids, and that routine diets do not provide sufficient protein to satisfy the needs of seriously burned children.

The effects of different types of dietary lipids were tested in burned guinea pigs. All diets were identical except for the type of lipid, with total energy intake from lipids equaling 10%. All animals received a 30% total body surface area (TBSA) flame burn and were fed identically by pump-controlled gastrostomy feedings for 14 days. When compared to safflower oil (74% linoleic acid) as well as linoleic acid alone, fish oil (18% eicosapentaenoic acid or EPA) administration resulted in less weight loss, better skeletal muscle mass, lower resting metabolic expenditure, better cell mediated immune responses, better opsonic indices, higher splenic weight, lower adrenal weight, higher serum transferrin, and lower serum C3 levels. With the exception of better cell mediated immune responses in the animals fed linoleic acid, the administration of indomethacin made little difference. These findings can be explained by a reduction in the synthesis of the dienoic prostaglandins that are derived from the omega 6 series of fatty acids, some of which are significantly immunosuppressive. Regulation of dietary lipids may be an important therapeutic advance in nutritional support after burn injury, and controlled trials should be considered.

Glutamine is essential for the function of lymphocytes and macrophages, where it serves, among other things, as a source of energy. Little information is available concerning the fuel that polymorphonuclear cells use for their metabolic and bactericidal functions. It was the purpose of this study to determine whether glutamine would enhance the in vitro bactericidal function of normal neutrophils and whether the amino acid would restore the observed impaired function in burn patients to or above the normal level. Twelve burn patients with total body surface area burns ranging from 32% to 87% were studied. At various postburn times, neutrophils were isolated and their ability to kill Staphylococcus aureus in the presence and absence of glutamine was determined and compared with that in normal subjects. Glutamine enhanced the bactericidal function of normal neutrophils. In every patient, at all but two postburn times, glutamine caused an improvement in the observed abnormal neutrophil bactericidal function and often restored it to or slightly above the normal level. Glutamine had no effect on the expression of C3b receptors (CR1 or CD35) or on phagocytosis by the cells. This study confirms the beneficial effects of glutamine in at least one arm of the immune system and adds evidence for the possible advantage of including this amino acid in the diets of burn and other trauma patients.

A sequential, prospective analysis of humoral and cellular immune function was performed on 20 burn patients with injuries involving >/=45% total body surface area. Infected patients had significantly worse neutrophil bactericidal activity against Staphylococcus aureus 502A than did noninfected patients. Chemotaxis of neutrophils correlated poorly with infection although chemotaxis was frequently abnormal. The opsonic index of serum was depressed early after the burn but returned to nearly normal values by the fourth to the fourteenth postburn day. There was no difference between infected and noninfected patients. Serum levels of IgG, properdin and C3, while initially low, remained within the normal range after the ninth postburn day in both groups. Factor B levels rose rapidly during the first three weeks after injury to more than double normal levels in many patients. Suggestive evidence for consumption of opsonic protein occurred with five of 19 episodes of bacteremia. The responsiveness of isolated lymphocytes to PHA was normal. However, patients' sera were shown to significantly inhibit the responsiveness of normal lymphocytes to PHA. Analysis of immunologic profiles for individual patients indicates that abnormalities of neutrophil function are the most important acquired defect predisposing patients to the development of bacteremia following major thermal injury; abnormalities of opsonic action play a secondary but important role.

Serum levels of properdin, Factor B and C3 and the ability of these sera to opsonize E. coli 075 were measured in 17 patients with surgical infections ranging in severity from mild to fatal. There was good direct correlation between severity of infection, serum levels of properdin and C3, and the ability of the serum to support opsonization. The levels of Factor B were not significantly reduced when measured by radial immunodiffusion, but immunoelectrophoresis showed conversion. Restoration of full opsonic activity was accomplished only by the addition of a combination of C3, Factor B, and properdin in excess. The findings provide evidence that severe bacterial infection causes a consumption of opsonic proteins which may result in a reduced ability of the patient's serum to opsonize bacteria and thereby further increase susceptibility to infection.