Effect of exogenous nitric oxide and superoxide on interleukin-8 from human polymorphonuclear leucocytes.
Patients with acute inflammatory lung injury are commonly treated with inhaled nitric oxide. Nitric oxide has profound immunoregulatory effects. Increased concentrations of the cytokine interleukin-8 (IL-8) in bronchoalveolar lavage fluid has been associated with disease severity. We have investigated the effects of a nitric oxide donor and a combined nitric oxide-superoxide donor on lipopolysaccharide-mediated accumulation of IL-8 from cultured human neutrophils. Interleukin-8 was measured in culture supernatant after 20 h using enzyme immunoassay. The combined nitric oxide-superoxide donor, 3-morpholinosydnonimine (SIN-1), dose-dependently decreased lipopolysaccharide-mediated IL-8 accumulation (P < 0.01). SIN-1 also decreased IL-8 accumulation from unstimulated neutrophils (P < 0.001). In contrast, the pure nitric oxide donor, 1,2,3,4-oxatriazolium 5-amino chloride (GEA-3162), increased stimulated IL-8 accumulation (P < 0.01) and also increased IL-8 accumulation in unstimulated cells (P < 0.002). Nitric oxide and superoxide have profound effects on IL-8. These results have important implications for the treatment of patients with acute lung injury with inhaled nitric oxide.
Cuthbertson
B H
BH
Academic Unit of Anaesthesia and Intensive Care, University of Aberdeen, UK.
Galley
H F
HF
Webster
N R
NR
D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D008070:Lipopolysaccharides / Q000276:immunology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
D016209:Interleukin-8; D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D013481:Superoxides; D009569:Nitric Oxide; C002385:linsidomine; C082874:GEA 3162; D008981:Molsidomine