TY - JOUR

T1 - Pronounced inflammatory response to endotoxaemia during nighttime

T2 - a randomised cross-over trial

AU - Alamili, Mahdi

AU - Bendtzen, Klaus

AU - Lykkesfeldt, Jens

AU - Rosenberg, Jacob

AU - Gögenur, Ismail

PY - 2014

Y1 - 2014

N2 - 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.DESIGN AND 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.CONCLUSION: 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.

AB - 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.DESIGN AND 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.CONCLUSION: 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.

KW - Adipokines

KW - Analysis of Variance

KW - Circadian Rhythm

KW - Cross-Over Studies

KW - Cytokines

KW - Endotoxemia

KW - Humans

KW - Inflammation

KW - Interleukin 1 Receptor Antagonist Protein

KW - Interleukin-10

KW - Interleukin-1beta

KW - Interleukin-6

KW - Lectins

KW - Lipopolysaccharides

KW - Male

KW - Malondialdehyde

KW - Oxidative Stress

KW - Receptors, Tumor Necrosis Factor

KW - Time Factors

KW - Tumor Necrosis Factor-alpha

U2 - 10.1371/journal.pone.0087413

DO - 10.1371/journal.pone.0087413

M3 - Journal article

C2 - 24475284

VL - 9

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e87413

ER -