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

CXC chemokines are chemotactic cytokines that specifically act on neutrophi ls. 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-pr oven 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 co ncentrations, 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 produ ced within the urinary tract, where they are involved in the recruitment of neutrophils to the urinary compartment.