Immunodepressive effects of LPS on monocyte CD14 in vivo

Having previously reported that septic patients displayed lower levels of monocyte CD14 (endotoxin receptor) as compared to normal individuals, we were interested in the hypothesis that lipopolysaccharide (LPS) modulates levels of monocyte CD14 in vivo. We examined CD14 expression in 13 human volunteers who were given a non-lethal injection of Escherichia coli LPS (4.0 ng/kg). Monocyte CD14 was assayed by direct immunofluorescent determination with appropriate anti-CD14 monoclonal antibodies using flow cytometry. To test for cell responsiveness, monocytes were additionally examined following in vitro stimulation by phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). Following LPS infusion, all patients displayed significant monocytopenia and responded with fever and tachycardia. Plasma samples demonstrated elevated levels of TNF alpha. CD14 expression was down-regulated by 52% on monocytes obtained 3 hr following LPS infusion (P < 0.05, vs. pre-LPS levels). Monocytes obtained pre-LPS infusion were down-regulated following in vitro stimulation by PMA to levels 72 +/- 8% and by FMLP to levels 75 +/- 5% of unstimulated control cells. In contrast, monocytes obtained 3 hr post-LPS infusion failed to respond to PMA or FMLP with significant down-regulation. LPS down-regulated CD14 expression on monocytes in vivo and LPS also blunted the ability of monocytes to respond to other stimuli. We conclude that LPS desensitizes monocytes to itself and thereby renders an immunodepressive effect on these cells.