IC14, an anti-CD14 antibody, inhibits endotoxin-mediated symptoms and inflammatory responses in humans

CD14 is a receptor for cell wall components of Gram-negative and Gram-posit ive bacteria that has been implicated in the initiation of the inflammatory response to sepsis, To determine the role of CD14 in LPS-induced effects i n humans, 16 healthy subjects received an i.v. injection of LPS (4 ng/kg) p receded (-2 h) by i.v. IC14, a recombinant chimeric mAb against human CD14, at a dose of 1 mg/kg over 1 h, or placebo. In subjects receiving IC14, sat uration of CD14 on circulating monocytes and granulocytes was >90% at the t ime of LPS injection. IC14 attenuated LPS-induced clinical symptoms and str ongly inhibited LPS-induced proinflammatory cytokine release, while only de laying the release of the anti-inflammatory cytokines soluble TNF receptor type I and IL-1 receptor antagonist. IC14 also inhibited leukocyte activati on, but more modestly reduced endothelial cell activation and the acute pha se protein response. The capacity of circulating monocytes and granulocytes to phagocytose Escherichia coli was only marginally reduced after infusion of IC14. These data provide the first proof of principle that blockade of CD14 is associated with reduced LPS responsiveness in humans in vivo.