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Immunomodulation by a combination of nitric oxide and glucocorticoids in a human endotoxin model


Dr Lars Hållström
Department of Anaesthesiology and Intensive Care
Karolinska University Hospital
S-141 86 Stockholm


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 2 h before administration of endotoxin (2 ng/kg). Thirty minutes later, GC (2 mg/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 (2 mg/kg) administrated after the endotoxin challenge could not modulate the systemic inflammatory response in this model of human experimental inflammation.