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Effects In Humans Of Intravenously Administered Endotoxin On Soluble Cell‐Adhesion Molecule And Inflammatory Markers: A Model Of Human Diseases
Author(s) -
Wilson Mf,
Blum R,
Dandona P,
Mousa Sa
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03463.x
Subject(s) - cell adhesion molecule , basal (medicine) , tumor necrosis factor alpha , medicine , inflammation , cell adhesion , endocrinology , e selectin , necrosis , cytokine , immunology , chemistry , cell , biology , biochemistry , insulin
SUMMARY 1. Endotoxin, a component of the cell wall of Gram‐negative bacteria, could be a predisposing mediator of many pathological disorders. The present study was undertaken to determine the effects and time‐course of acute endotoxin challenge on inflammatory and cell‐adhesion molecule markers shedding in the plasma as potential surrogates. 2. Six normal male subjects per group (age range 21–35 years) were injected with 4 ng/kg, i.v., reference standard Escherichia coli (0113:h10:k) endotoxin or physiological saline. 3. Plasma inflammatory markers (tumour necrosis factor (TNF)‐ α , interleukin (IL)‐6 and TNF‐receptor I (RI)) and cell‐adhesion molecule markers (soluble L‐selectin, soluble P‐selectin, soluble vascular cell adhesion molecule (VCAM)‐1) were determined using sensitive and specific ELISA. 4. Tumour necrosis factor‐ α increased from a basal level of 2.8 pg/mL to approximately 800 pg/mL at 90 min after endotoxin. Similarly, IL‐6 peaked 2–3 h after endotoxin injection, with a rapid decline by 6–8 h, and levels returned to basal values by 24 h. 5. In contrast, TNF‐RI peaked at 2 h (increasing from basal levels of 900–3300 pg/mL) with a much slower decline and without return to basal levels at 24 h (1400 pg/mL). 6. Endotoxin resulted in a rapid rise in soluble L‐selectin within 1 h, which increased from a basal of 150–425 ng/mL. This rapid rise in soluble L‐selectin was sustained for up to 2.5 h and then rapidly declined to basal levels by 3.5 h. 7. In contrast, plasma soluble P‐selectin levels showed a delayed and progressive increase up to 8 h (increasing from a basal level of 50–95 ng/mL), with a partial decline at 24 h (80 ng/mL). 8. Similarly, soluble VCAM‐1 levels showed a progressive rise up to 24 h (increasing from basal values of 600–1000 ng/mL). 9. This acute human model of endotoxin exposure demonstrated an upregulation of inflammatory stimuli leading to a short‐term hyperactivation of leucocytes and a more sustained activation of platelets and endothelium. 10. This model provides a non‐invasive method for studying the complex effects of endotoxin‐like pathogens on different cellular events using soluble plasma surrogate markers.