Publication Date:
2006-11-16
Description:
Background: The Duffy receptor is a promiscuous receptor for chemokines that binds selected members of both the C-X-C and C-C families with high affinity. Duffy antigen may influence plasma levels of proinflammatory cytokines by acting as a “chemokine sink”. Additionally, Duffy knockout mice experienced an exaggerated response to endotoxin in comparison to wild-type mice. The current trial was designed to elucidate the functional role of the Duffy blood group antigen in human inflammation. We hypothesized that “Duffy negative“ volunteers might show an increased inflammatory response to endotoxin (LPS) infusion in terms of cytokine response. The human endotoxemia model is a well established model of systemic inflammation, where a well defined, self-limited inflammatory stimulus permits the elucidation of key players involved in the inflammatory response. We therefore used this model to investigate the functional role of the Duffy Antigen Receptor Complex (DARC) in the inflammatory response after endotoxin challenge. Methods: Thirty-two healthy male volunteers received an intravenous infusion of 2ng/kg endotoxin, 16 Caucasians (Duffy antigen positive on erythrocytes) and 16 subjects of African descent (“Duffy negatives”). Cytokines, chemokines, as well as their receptors were quantified by ELISA, RT-PCR and FACS. Results: Plasma levels of TNF, IL-6, IL-8 and IL-8 mRNA in whole blood increased to a similar extent in both groups after LPS infusion. In contrast, peak MCP-1 levels at 3 hours were roughly 2-fold higher in Duffy positive subjects 16ng/mL as compared to Duffy negative subjects (7ng/mL p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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