Reduced ex vivo chemokine production by polymorphonuclear cells after in vivo exposure of normal humans to endotoxin.
Monocytes from patients with sepsis have a reduced capacity to produce cytokines, a state referred to as immunoparalysis. To determine whether polymorphonuclear leukocytes (PMNL) can be rendered hyporesponsive, PMNL from 6 healthy volunteers intravenously challenged with lipopolysaccharide (LPS; 4 ng/kg) were stimulated ex vivo with heat-killed bacteria or LPS, and the release of the CXC chemokines interleukin-8, epithelial-derived neutrophil attractant-78, and growth-related oncogen-alpha was measured. At 1 and 2 h after LPS administration in vivo, PMNL produced fewer CXC chemokines after stimulation with bacteria or LPS (all P<.05). Serum obtained 2 h after in vivo administration of LPS did not influence chemokine production by PMNL from 6 healthy volunteers not previously exposed to LPS. Thus, intravenous injection of LPS induces a refractory state of PMNL that is not caused by soluble factors produced in response to in vivo exposure to LPS.
Schultz
M J
MJ
Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. m.j.schultz@amc.uva.nl
Olszyna
D P
DP
de Jonge
E
E
Verbon
A
A
van Deventer
S J
SJ
van der Poll
T
T
D000328:Adult; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines / Q000096:biosynthesis / Q000097:blood*; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000097:blood; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000097:blood; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D006133:Growth Substances / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004731:Endotoxins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides