Pronounced inflammatory response to endotoxaemia during nighttime: a randomised cross-over trial.
BACKGROUND
Circadian variation in bodily functions has been shown to impact health in acute and chronic medical conditions. Little is known about the relationship between circadian rhythm and sepsis in humans. We aimed to investigate circadian variations in the host response in a human endotoxaemia model.


METHODS
A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS) 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF)-alpha, soluble TNF receptors (sTNF-R)-1 and -2, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, and IL-10 as well as YKL-40 and the oxidative stress markers malondialdehyde (MDA), ascorbic acid (AA) and dehydroascorbic acid (DHA) before and at 2, 4, 6 and 8 hours after LPS administration.


RESULTS
The levels of MDA and IL-10 where significantly higher during the day time (P<0.05) whereas levels of TNF-alpha, sTNF-RI, sTNF-RII, IL-1Ra, IL-6, and YKL-40 were higher (P<0.01 for all comparisons) during the night time. No significant differences were seen in the levels of AA and DHA.


CONCLUSIONS
A day-night difference in the acute phase response to endotoxaemia exists in healthy volunteers with a more pronounced inflammatory response during the night time. This circadian difference in the response to endotoxaemia may play an important role in the clinical setting and should be investigated further.
Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Herlev, Denmark.
Mahdi
M
Alamili
Institute for Inflammation Research, Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet, Denmark.
Klaus
K
Bendtzen
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jens
J
Lykkesfeldt
Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Herlev, Denmark.
Jacob
J
Rosenberg
Department of Surgical Gastroenterology, University of Copenhagen, Herlev Hospital, Herlev, Denmark.
Ismail
I
Gögenur
D054392:Adipokines / Q000097:blood; D000704:Analysis of Variance; D000071451:Chitinase-3-Like Protein 1; D002940:Circadian Rhythm / Q000502:physiology*; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D037102:Lectins / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D037102:Lectins; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008315:Malondialdehyde