Endogenous Tetrapyrroles Influence Leukocyte Responses to Lipopolysaccharide in Human Blood

Autor(en)

Kavita Bisht, Jens Tampe, Cecilia Shing, Bhavisha Bakrania, James Winearls, John Fraser, Karl-Heinz Wagner, Andrew C Bulmer

Abstrakt

Sepsis is associated with abnormal host immune function in response to pathogen exposure, including endotoxin (lipopolysaccharide; LPS). Cytokines play crucial roles in the induction and resolution of inflammation in sepsis. Therefore, the primary aim of this study was to investigate the effects of endogenous tetrapyrroles, including biliverdin (BV) and unconjugated bilirubin (UCB) on LPS-induced cytokines in human blood. Biliverdin and UCB are by products of haem catabolism and have strong cytoprotective, antioxidant and anti-inflammatory effects. In the present study, whole human blood supplemented with BV and without was incubated in the presence or absence of LPS for 4 and 8 hours. Thereafter, whole blood was analysed for gene and protein expression of cytokines, including IL-1β, IL-6, TNF, IFN-γ, IL-1Ra and IL-8. Biliverdin (50 μM) significantly decreased the LPS-mediated gene expression of IL-1β, IL-6, IFN-γ, IL-1Ra and IL-8 (P<0.05). Furthermore, BV significantly decreased LPS-induced secretion of IL-1β and IL-8 (P<0.05). Serum samples from human subjects and, wild type and hyperbilirubinaemic Gunn rats were also used to assess the relationship between circulating bilirubin and cytokine expression/production. Significant positive correlations between baseline UCB concentrations in human blood and LPS-mediated gene expression of IL-1β (R=0.929), IFN-γ (R=0.809), IL-1Ra (R=0.786) and IL-8 (R=0.857) were observed in blood samples (all P<0.05). These data were supported by increased baseline IL-1β concentrations in hyperbilirubinaemic Gunn rats (P<0.05). Blood samples were also investigated for complement receptor-5 (C5aR) expression. Stimulation of blood with LPS decreased gene expression of C5aR (P<0.05). Treatment of blood with BV alone and in the presence of LPS tended to decrease C5aR expression (P=0.08). These data indicate that supplemented BV inhibits the ex vivo response of human blood to LPS. Surprisingly, however, baseline UCB was associated with heighted inflammatory response to LPS. This is the first study to explore the effects of BV in a preclinical human model of inflammation and suggests that BV could represent an anti-inflammatory target for the prevention of LPS mediated inflammation in vivo.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Griffith University, University of Tasmania, Gold Coast University Hospital, University of Queensland

Journal

Journal of Clinical & Cellular Immunology

Band

5

Seiten

1000218

ISSN

2155-9899

DOI

https://doi.org/10.4172/2155-9899.1000218

Publikationsdatum

05-2014

Peer-reviewed

Ja

ÖFOS 2012

303009 Ernährungswissenschaften

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/endogenous-tetrapyrroles-influence-leukocyte-responses-to-lipopolysaccharide-in-human-blood(62522090-9c27-4403-9f7b-c41af3c7d660).html