Neutrophil dysfunction: The cellular mechanism of impaired immunity during total parenteral nutrition in infancy

Background: Studies have shown that total parenteral nutrition (TPN) in infancy is associated with impaired immunity. The causes of this acquired immunodeficiency are poorly understood. Bacterial infection is a major complication of TPN suggesting neutrophils may be affected by this feeding modality. Purpose: The aim of this study was to test the hypothesis that TPN-related impaired bactericidal activity is related to impairment of neutrophil function, particularly intracellular killing. Methods: Studies were performed in five infants (age <2 months) who received long-term TPN (>10 days), five control infants who received a normal enteral diet, and five healthy adults. Patients on long-term TPN were clinically stable with no evidence of sepsis. The experimental study used an in vitro whole-blood model of septicaemia. Coagulase-negative staphylococci were the bacterial challenge. Whole-blood killing of coagulase-negative staphylococci was measured after 45 minutes using the Miles-Misra technique. Neutrophils were separated from whole blood after 15, 30, 45, and 60 minutes of bacterial challenge. The survival rate of the bacteria within the neutrophils was analysed by flow cytometry and the percentage of the bacteria killed by neutrophil intracellular killing assessed at each time-point. Results: Whole-blood killing was significantly lower (P =.05) in infants who received long-term TPN (33.3%) compared with control infants (69.7%) and adults (67.7%). In all subjects studied, neutrophil intracellular killing increased with incubation time. At each time point the intracellular killing in infants on long-term TPN was significantly lower (P<.05) than in normal central infants and adults. Conclusion: Future strategies to prevent TPN-related infection should aim to minimise this acquired neutrophil dysfunction.