TY - JOUR
T1 - Effect of exogenous nitric oxide and superoxide on interleukin-8 from human polymorphonuclear leucocytes
AU - Cuthbertson, Brian H.
AU - Galley, Helen F.
AU - Webster, Nigel R.
PY - 1997/1/1
Y1 - 1997/1/1
N2 - 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 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.
AB - 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 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.
KW - Lung, adult respiratory distress syndrome
KW - Lung, damage
KW - Pharmacology, nitric oxide
KW - Polypeptides, cytokines
UR - http://www.scopus.com/inward/record.url?scp=0031009377&partnerID=8YFLogxK
U2 - 10.1093/bja/78.6.714
DO - 10.1093/bja/78.6.714
M3 - Article
C2 - 9215025
AN - SCOPUS:0031009377
SN - 0007-0912
VL - 78
SP - 714
EP - 717
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
IS - 6
ER -