BACKGROUND: The systemic inflammatory response to infection (sepsis) involves widespread organ dysfunction, including changes in immune modulation, cardiovascular derangements, and neural activation. Two neuropeptide/receptor systems, nociceptin/orphanin FQ (N/OFQ) which acts at the non-classical opioid receptor NOP and urotensin-II (U-II) which acts at the urotensin receptor (UT), have been implicated in neural, immune, and cardiovascular system function. In this study, we make measurements of these peptides in critically ill patients. METHODS: Plasma samples from 21 critically ill patients with sepsis were collected over four consecutive days. Plasma N/OFQ and U-II concentrations were determined by radioimmunoassay and compared with biochemical and clinical markers of illness severity, including serum creatinine, bilirubin, platelet and white cell counts, admission APACHE II and serial SOFA scores. RESULTS: Median (inter-quartile range) admission plasma N/OFQ concentrations in sepsis were higher in patients who died within 30 days (n=4) compared with survivors (n=17); 3.0 (2.5-5.0) vs 1.0 (1.0-2.5) pg ml(-1) (P=0.028). Plasma N/OFQ concentrations were increased in a subgroup of five patients who had undergone major gastrointestinal surgery. There were no significant changes in plasma U-II concentrations. There were no correlations between plasma U-II and N/OFQ concentrations and markers of illness severity and organ system dysfunction. CONCLUSIONS: Plasma N/OFQ concentrations were increased in critically ill patients with sepsis who had undergone major gastrointestinal surgery and in patients who subsequently died. Further work is required to clarify the significance of plasma N/OFQ concentrations in sepsis.
BACKGROUND: The systemic inflammatory response to infection (sepsis) involves widespread organ dysfunction, including changes in immune modulation, cardiovascular derangements, and neural activation. Two neuropeptide/receptor systems, nociceptin/orphanin FQ (N/OFQ) which acts at the non-classical opioid receptor NOP and urotensin-II (U-II) which acts at the urotensin receptor (UT), have been implicated in neural, immune, and cardiovascular system function. In this study, we make measurements of these peptides in critically ill patients. METHODS: Plasma samples from 21 critically ill patients with sepsis were collected over four consecutive days. Plasma N/OFQ and U-II concentrations were determined by radioimmunoassay and compared with biochemical and clinical markers of illness severity, including serum creatinine, bilirubin, platelet and white cell counts, admission APACHE II and serial SOFA scores. RESULTS: Median (inter-quartile range) admission plasma N/OFQ concentrations in sepsis were higher in patients who died within 30 days (n=4) compared with survivors (n=17); 3.0 (2.5-5.0) vs 1.0 (1.0-2.5) pg ml(-1) (P=0.028). Plasma N/OFQ concentrations were increased in a subgroup of five patients who had undergone major gastrointestinal surgery. There were no significant changes in plasma U-II concentrations. There were no correlations between plasma U-II and N/OFQ concentrations and markers of illness severity and organ system dysfunction. CONCLUSIONS: Plasma N/OFQ concentrations were increased in critically ill patients with sepsis who had undergone major gastrointestinal surgery and in patients who subsequently died. Further work is required to clarify the significance of plasma N/OFQ concentrations in sepsis.
Authors: Shailendra R Singh; Nikol Sullo; Maria Matteis; Giuseppe Spaziano; John McDonald; Ruth Saunders; Lucy Woodman; Konrad Urbanek; Antonella De Angelis; Raffaele De Palma; Rachid Berair; Mitesh Pancholi; Vijay Mistry; Francesco Rossi; Remo Guerrini; Girolamo Calò; Bruno D'Agostino; Christopher E Brightling; David G Lambert Journal: Br J Pharmacol Date: 2016-03-06 Impact factor: 8.739
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Authors: Mohamed Farrag; Lacee J Laufenberg; Jennifer L Steiner; Gregory E Weller; Charles H Lang; Victor Ruiz-Velasco Journal: PLoS One Date: 2015-05-27 Impact factor: 3.240
Authors: Jonathan P Thompson; Alcira Serrano-Gomez; John McDonald; Nadia Ladak; Sarah Bowrey; David G Lambert Journal: PLoS One Date: 2013-10-04 Impact factor: 3.240
Authors: Zoë L S Brookes; Emily N Stedman; Nicola J Brown; Christopher P Hebbes; Remo Guerrini; Girolamo Calo; Charles S Reilly; David G Lambert Journal: PLoS One Date: 2013-09-23 Impact factor: 3.240