title: Hormone and Cytokine Responses to Repeated Endotoxin Exposures-No Evidence of Endotoxin Tolerance After 5 Weeks in Humans.
abstract: Endotoxin administrations are used in experimental models of inflammatory disease. Short-term endotoxin tolerance in response to repeated endotoxin exposure is well known, but the duration of endotoxin tolerance in humans remains unknown. The main purpose of this study was to test whether endotoxin tolerance is present in vivo when separating endotoxin exposures with more than 5 weeks, a time span often used between individual investigations in clinical experimental studies. Seventeen healthy young men were exposed twice to Escherichia coli endotoxin. The inflammatory response was calculated as area under the curve between the first and second endotoxin exposures for heart rate, mean arterial blood pressure, temperature, cortisol, tumor necrosis factor α, and interleukin (IL)-1β, IL-6, and IL-10. The median interval between exposures was 90 days (range, 37-244). The ratio between the inflammatory responses during the second and the first endotoxin exposures was 0.89 ± 0.09 (P = 0.28) for tumor necrosis factor α, 0.96 ± 0.07 (P = 0.53) for IL-1β, 0.97 ± 0.11 (P = 0.78) for IL-6, 1.30 ± 0.18 (P = 0.12) for IL-10, and 0.92 ± 0.04 (P = 0.10) for cortisol. Our data do not show evidence of in vivo tolerance to repeated endotoxin exposure when administrations are separated with at least 5 weeks. This observation is important in the planning and interpretation of future experimental endotoxin studies.
authors.affiliation: *Department of Internal Medicine and Endocrinology, and Medical Research Laboratories, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; and †Department of Medicine, Viborg Regional Hospital, Viborg, Denmark.
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Rittig
authors.forename: Henrik H
authors.initials: HH
authors.lastname: Thomsen
authors.forename: Ermina
authors.initials: E
authors.lastname: Bach
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000737:chemistry / Q000633:toxicity*; D004926:Escherichia coli / Q000737:chemistry*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D013997:Time Factors
chemical_list: D016207:Cytokines; D004731:Endotoxins; D006854:Hydrocortisone