title: Chemotactic activity of CXC chemokines interleukin-8, growth-related oncogene-alpha, and epithelial cell-derived neutrophil-activating protein-78 in urine of patients with urosepsis.
abstract: CXC chemokines are chemotactic cytokines that specifically act on neutrophils. To obtain insight into the extent of local production of CXC chemokines during acute pyelonephritis, interleukin (IL)-8, growth-related oncogene (GRO)-alpha, and epithelial cell-derived neutrophil-activating protein (ENA)-78 were measured in urine and plasma samples from patients with culture-proven urosepsis (n=33), healthy human control subjects with sterile urine (n=31), and human volunteers intravenously injected with endotoxin (n=11). Patients had profoundly elevated urine concentrations of chemokines with no (GRO-alpha and ENA-78) or little (IL-8) elevation in plasma. Endotoxin-challenged subjects demonstrated transient increases in plasma chemokine concentrations, with no (GRO-alpha) or little (IL-8 and ENA-78) elevation in urine. Urine from patients exerted chemotactic activity toward neutrophils, which was partially inhibited by neutralizing antibodies against IL-8, GRO-alpha, or ENA-78. During urosepsis, CXC chemokines are predominantly produced within the urinary tract, where they are involved in the recruitment of neutrophils to the urinary compartment.
authors.affiliation: Academic Medical Center, Dept. of Experimental Internal Medicine, 1105 AZ Amsterdam, The Netherlands. dariuszolszyna@rocketmail.com
authors.forename: D P
authors.initials: DP
authors.lastname: Olszyna
authors.forename: S M
authors.initials: SM
authors.lastname: Opal
authors.forename: J M
authors.initials: JM
authors.lastname: Prins
authors.forename: D L
authors.initials: DL
authors.lastname: Horn
authors.forename: P
authors.initials: P
authors.lastname: Speelman
authors.forename: S J
authors.initials: SJ
authors.lastname: van Deventer
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000208:Acute Disease; D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000097:blood / Q000276:immunology / Q000652:urine*; D004731:Endotoxins / Q000008:administration & dosage; D006133:Growth Substances / Q000097:blood / Q000276:immunology / Q000652:urine*; D006801:Humans; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000652:urine*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects; D011704:Pyelonephritis / Q000652:urine*
chemical_list: D000906:Antibodies; C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D004731:Endotoxins; D006133:Growth Substances; D016209:Interleukin-8