Open Access

ARTICLE

Effect of IC14, an anti-CD14 antibody, on plasma and cell-associated chemokines during human endotoxemia

Dariusz P. Olszyna^1,2, Annelies Verbon², John P. Pribble³, Terence Turner³, Tim Axtelle³, Sander J. H. van Deventer¹, Tom van der Poll^1,2

Department of Experimental Internal Medicine1 , Department of Infectious Diseases, Tropical Medicine and AIDS2 , Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands, ICOS Corporation3 , Bothell, WA, USA.

* Corresponding Author: Tom van der Poll,

European Cytokine Network 2003, 14(3), 158-162.

Abstract

To determine the role of CD14 in lipopolysaccharide (LPS)-induced release of chemokines, 16 humans were injected with LPS (4 ng/kg) preceded (– 2 h) by intravenous IC14, an anti-human CD14 monoclonal antibody, or placebo. LPS elicited increases in interleukin (IL)-8 concentrations in plasma and in lysates of red blood cell (RBC), polymorphonuclear cell and mononuclear cell fractions, which were all reduced by IC14. LPS also induced rises in the plasma and RBC levels of monocyte chemoattractant protein (MCP)-1, which were diminished by IC14. Macrophage inflammatory protein (MIP)-1a and MIP-1β, chemokines that in contrast to IL-8 and MCP-1 can not bind to the Duffy antigen receptor for chemokines on RBCs, were only detected in plasma. IC14 attenuated the LPS-induced release of MIP-1b, but not of MIP-1α. IL-8 and MCP-1, but not MIP-1α and MIP-1β, circulate in RBC-associated form during endotoxemia. LPS-induced chemokine release is, in part, mediated by an interaction with CD14.

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Keywords

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