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

• Published in: Acta anaesthesiologica Scandinavica Vol. 55; no. 1; pp. 20 - 27
• Main Authors: HÅLLSTRÖM, L., BERGHÄLL, E., FROSTELL, C., SOLLEVI, A., SOOP, A. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2011; Blackwell
• Subjects: Administration, Inhalation; Adult; Anaesthesiology and Intensive Care; Anestesiologi och intensivvård; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood Cell Count; Body Temperature - drug effects; Cross-Over Studies; Cytokines - blood; Double-Blind Method; Endotoxemia - metabolism; Endotoxemia - pathology; Endotoxins - toxicity; Female; Glucocorticoids - administration & dosage; Glucocorticoids - pharmacology; Heart Rate - drug effects; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - pharmacology; Immunomodulation - drug effects; Inflammation - chemically induced; Inflammation - pathology; Injections, Intravenous; Male; Medical sciences; Medicin och hälsovetenskap; Nitric Oxide - administration & dosage; Nitric Oxide - pharmacology; Young Adult; Human; Toxin; Immunomodulation; Nitric oxide; Anesthesia; Endotoxin; Glucocorticoid
• ISSN: 0001-5172; 1399-6576; 1399-6576
• DOI: 10.1111/j.1399-6576.2010.02297.x

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.