Decreased exhaled nitric oxide as a marker of postinsult immune paralysis.
Nitric oxide (NO) regulates neutrophil migration and alveolar macrophage functions such as cytokine synthesis and bacterial killing, both of which are impaired in immune paralysis associated with critical illness. The aim of this study was to determine whether NO is involved in immune paralysis and whether exhaled NO measurement could help to monitor pulmonary defenses. NO production (protein expression, enzyme activity, end products, and exhaled NO measurements) was assessed in rats after cecal ligation and puncture to induce a mild peritonitis (leading to approximately 20% mortality rate). An early and sustained decrease in exhaled NO was found after peritonitis (from 1 to 72 h) compared with healthy rats [median (25th-75th percentile), 1.5 parts per billion (ppb) (1.2-1.7) vs. 4.0 ppb (3.6-4.3), P < 0.05], despite increased NO synthase-2 and unchanged NO synthase-3 protein expression in lung tissue. NO synthase-2 activity was decreased in lung tissue. Nitrites and nitrates in supernatants of isolated alveolar macrophages decreased after peritonitis compared with healthy rats, and an inhibitory experiment suggested arginase overactivity in alveolar macrophages bypassing the NO substrate. Administration of the NO synthase-2 inhibitor aminoguanidine to healthy animals reproduced the decreased neutrophil migration toward alveolar spaces that was observed after peritonitis, but L-arginine administration after peritonitis failed to correct the defect of neutrophil emigration despite increasing exhaled NO compared with D-arginine administration [4.8 (3.9-5.7) vs. 1.6 (1.3-1.7) ppb, respectively, P < 0.05]. In conclusion, the decrease in exhaled NO observed after mild peritonitis could serve as a marker for lung immunodepression.
Attalah
Habiba L
HL
Institut National de la Santé et de la Recherche Medicale U492-Université Paris XII, France.
Honoré
Stéphanie
S
Eddahibi
Saadia
S
Marcos
Elisabeth
E
Soussy
Claude-James
CJ
Adnot
Serge
S
Delclaux
Christophe
C
D000818:Animals; D001119:Arginase / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods; D045853:Exhalation / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology*; D008168:Lung / Q000201:enzymology / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D009569:Nitric Oxide / Q000032:analysis* / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000097:blood / Q000276:immunology; D010538:Peritonitis / Q000150:complications / Q000175:diagnosis* / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001119:Arginase