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Background: Neutrophil dysfunction has been documented after injury in animals and human beings. This review evaluates the relative effects of the hormonal and endotoxin response to injury on immune resistance., Method: Review of the pertinent English-language literature., Results: In volunteers given total parenteral nutrition, neutrophils demonstrate a robust response to leukotriene B4 but none to zymosan/activated serum or the bacterial metabolite formyl-methionyl-leucyl-phenylalanine (FMLP). This finding suggests subclinical exposure to activated complement and FMLP that does not occur during enteral feeding. Additional evidence of neutrophil activation is the release of lactoferrin to the same degree with the two routes of feeding. When normal volunteers are challenged with endotoxin, uniform impairment of the neutrophil response to chemotactic stimuli except LTB4 is demonstrated. Epinephrine increases the total circulating neutrophil pool for a few hours, whereas when cortisol is administered, the neutrophil counts continue to increase through 6 h. A combined epinephrine and cortisol infusion extends the half-life of neutrophils. The role of genomic and central nervous system control through the vagus nerve also is reviewed., Conclusion: Normal volunteers have provided insight into the stress response to infection that is understood only partially.