Endotoxin down-regulates monocyte and granulocyte interleukin-6 receptors without influencing gp130 expression in humans.
Interleukin (IL)-6 is important for host defense against various pathogens. The IL-6 receptor (IL-6R) complex consists of a ligand-binding component (IL-6R) and a signal-transducing component (gp130). In a study designed to obtain insight into the regulation of this receptor complex during inflammation, 8 healthy subjects received an intravenous injection of lipopolysaccharide (LPS; 4 ng/kg), and receptor expression was determined on blood leukocytes by use of fluorescence-activated cell cytometry. LPS induced a transient decrease in monocyte and granulocyte IL-6R expression but did not influence gp130. The plasma concentrations of soluble IL-6R and soluble gp130 did not change after LPS administration. Expression of the receptor for leukemia inhibitory factor, a member of the IL-6R family, remained unaltered after LPS injection. In whole blood in vitro, LPS and gram-positive stimuli and proinflammatory cytokines were capable of down-modulating the IL-6R. Monocytes and granulocytes may down-regulate IL-6R at their surface upon their first interaction with bacterial antigens.
Dekkers
P E
PE
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. P.E.Dekkers@amc.uva.nl
Juffermans
N P
NP
ten Hove
T
T
de Jonge
E
E
van Deventer
S J
SJ
van der Poll
T
T
D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D050822:Cytokine Receptor gp130; D015536:Down-Regulation; D019446:Endotoxemia / Q000378:metabolism; D006098:Granulocytes / Q000737:chemistry / Q000187:drug effects*; D006131:Growth Inhibitors / Q000097:blood; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides / Q000633:toxicity*; D008222:Lymphokines / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects*; D019947:Receptors, Interleukin-6 / Q000097:blood*
D015703:Antigens, CD; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides; D008222:Lymphokines; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130