Dose-related negative affect arousal following intravenous endotoxin in humans: An evaluation of a new Clinical Center Reference Endotoxin (CCRE) of Escherichia coli (E. coli group O 113:H10:K negative) in healthy volunteers

We evaluated dose-related negative affect (NA) responses to a new reference lot of endotoxin E. coli (LPS) administered as an IV bolus in 23 healthy subjects (age 18–40 yr., 23% female, 50% minorities). Subjects were randomly assigned to one of 4-dose groups with each group comprised of 6 subjects [4 receiving endotoxin, 2 receiving normal saline]. Group 1 received 0.6 ng/kg; Group 2-1 ng/kg; Group 3-2 ng/kg; and Group 4-4 ng/kg doses of LPS. NA was assessed prior to dosing, at 90- and 180-min after dosing. We used the Patient Health Questionnaire (PHQ-9) to assess depressive symptoms prior to dosing. Adjusting for potential confounders, results revealed a significant Dose X Period interaction (F = 2.53, adjusted p