Immunomodulation by a combination of nitric oxide and glucocorticoids in a human endotoxin model.
BACKGROUND
inflammatory reactions arise in reaction to a variety of pathogenic insults. The combination of inhaled nitric oxide (iNO) and glucocorticoids (GC) may attenuate endotoxin-induced inflammatory responses. It has been shown that the combination of iNO (30 p.p.m.) and steroids blunted the inflammatory response in a porcine endotoxin model, but not in humans. Therefore, we investigated whether a clinically 'maximal' dose of iNO in combination with GC could modulate the systemic inflammatory response in a human endotoxin model.


METHODS
a double-blind, cross-over, placebo-controlled randomized study including 15 healthy Caucasian volunteers (five females, 10 males). Performed at the Intensive Care Unit in a university hospital. iNO 80 p.p.m. or placebo (nitrogen) was started 2h before administration of endotoxin (2 ng/kg). Thirty minutes later, GC (2mg/kg, hydrocortisone) was administered intravenously. Blood samples and clinical signs were collected before and up to 24 h after the endotoxin injection.


RESULTS
body temperature and heart rate increased significantly subsequent to endotoxin challenge. The plasma levels of IFN-γ, IL-1β, IL-2, 4 5, 6, 8, 10, 12, 13 and TNFα were markedly elevated. However, HMGB-1 and sRAGE were unaffected. No difference between placebo/GC and iNO/GC treatment was observed in the clinical or cytokine response, neither was there any difference between the first and the second exposure to endotoxin.


CONCLUSIONS
pre-treatment with iNO 80 p.p.m. along with GC (2mg/kg) administrated after the endotoxin challenge could not modulate the systemic inflammatory response in this model of human experimental inflammation.
Hållström
L
L
Departments of Clinical Science Intervention, Anesthesiology and Intensive Care Medicine, Karolinska University Hospital, Huddinge and Solna, Karolinska Institutet, Stockholm, Sweden. lars.hallstrom@karolinska.se
Berghäll
E
E
Frostell
C
C
Sollevi
A
A
Soop
A L
AL
D000280:Administration, Inhalation; D000328:Adult; D001772:Blood Cell Count; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology*; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology; D056747:Immunomodulation / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
D016207:Cytokines; D004731:Endotoxins; D005938:Glucocorticoids; D009569:Nitric Oxide; D006854:Hydrocortisone