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 cyto kines, a state referred to as immunoparalysis. To determine whether polymor phonuclear leukocytes (PMNL) can be rendered hyporesponsive, PMNL from 6 he althy volunteers intravenously challenged with lipopolysaccharide (LPS; 4 n g/kg) were stimulated ex vivo with heat-killed bacteria or LPS, and the rel ease of the CXC chemokines interleukin-8, epithelial-derived neutrophil att ractant-78, and growth-related oncogen-alpha was measured. At 1 and 2 h aft er LPS administration in vivo, PMNL produced fewer CXC chemokines after sti mulation with bacteria or LPS (all P < .05). Serum obtained 2 h after in vi vo administration of LPS did not influence chemokine production by PMNL fro m 6 healthy volunteers not previously exposed to LPS. Thus, intravenous inj ection of LPS induces a refractory state of PMNL that is not caused by solu ble factors produced in response to in vivo exposure to LPS.