Dopaminergic Control of Inflammation and Glycemia in Sepsis and Diabetes

Frontiers in Immunology
Eleonora FeketeovaLuis Ulloa

Abstract

Most preclinical treatments for sepsis failed in clinical trials in part because the experimental models of sepsis were performed on healthy animals that do not mimic septic patients. Here, we report that experimental diabetes worsens glycemia, inflammation, and mortality in experimental sepsis. Diabetes increases hyperglycemia, systemic inflammation, and mortality in sepsis. Diabetes exacerbates serum tumor necrosis factor (TNF) levels in sepsis by increasing splenic TNF production. Both serum from diabetic mice and glucose increase cytokine production in splenocytes. Anti-inflammatory treatments cannot control hyperglycemia and are less effective in diabetic patients. By contrast, dopaminergic agonist type-1, fenoldopam, attenuates hyperglycemia, and systemic inflammation in diabetic septic mice by inhibiting splenic p65NF-kB phosphorylation. Fenoldopam inhibits TNF production in splenocytes even at high glucose concentrations and inhibits the canonical NF-kB pathway by inhibiting p65RelA and p50NF-kB1 phosphorylation without affecting the non-canonical NF-kB proteins. Treatment with fenoldopam rescues diabetic mice from established polymicrobial peritonitis even when the treatment is started after the onset of sepsis. These ...Continue Reading

References

Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Jan 1, 1993·Annual Review of Neuroscience·J A Gingrich, M G Caron
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·T S DoiY Obata
Jan 24, 2002·The Journal of Experimental Medicine·Elizabeth AlcamoDavid Baltimore
Oct 3, 2002·Nature Reviews. Immunology·Qiutang Li, Inder M Verma
Dec 20, 2002·Nature·Carl Nathan
Jan 10, 2003·The New England Journal of Medicine·Richard S Hotchkiss, Irene E Karl
May 2, 2003·Nature Medicine·Niels C RiedemannPeter A Ward
Jan 13, 2004·Nature Medicine·Ji-Jing YanDong-Keun Song
Jun 12, 2004·The Journal of Investigative Dermatology·Ghada NaguibDana T Graves
Jan 22, 2005·Annual Review of Medicine·Todd W Rice, Gordon R Bernard
Feb 3, 2005·Nature Medicine·Melek C ArkanMichael Karin
Feb 8, 2005·Trends in Molecular Medicine·Luis Ulloa, Kevin J Tracey
Mar 26, 2005·Journal of Dental Research·D T GravesE Krall
Aug 2, 2005·Nature Reviews. Drug Discovery·Luis Ulloa
Oct 15, 2005·Nature Reviews. Drug Discovery·Jon A BurasMichail Sitkovsky
Dec 13, 2005·The Journal of Clinical Investigation·Stuart P WeisbergAnthony W Ferrante
Apr 4, 2006·Intensive Care Medicine·Reiner OberbeckMichael S Exton
Jul 18, 2006·Microbes and Infection·Manuela PulitiLuciana Tissi
Oct 31, 2006·Oncogene·M S HaydenS Ghosh
Jul 27, 2007·JAMA : the Journal of the American Medical Association·Derek C Angus
May 17, 2008·Biochimica Et Biophysica Acta·Jane E Carré, Mervyn Singer
Dec 31, 2008·Critical Care Medicine·Pedro R PóvoaUNKNOWN Portuguese Community-Acquired Sepsis Study Group
Mar 26, 2009·The New England Journal of Medicine·Simon FinferJuan J Ronco
May 15, 2009·Critical Care : the Official Journal of the Critical Care Forum·Luis Ulloa, Edwin A Deitch
Sep 3, 2009·World Journal of Gastroenterology : WJG·Hiroyuki HirasawaMasataka Nakamura
Sep 30, 2010·The Journal of Clinical Investigation·Aliki KosteliAnthony W Ferrante
Feb 23, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gergely VidaLuis Ulloa

❮ Previous
Next ❯

Citations

Feb 1, 2019·Scientific Reports·Biju JosephLuis Ulloa
Nov 6, 2018·Brain, Behavior, and Immunity·Guilherme ShimojoLuis Ulloa
Feb 18, 2020·Neuroscience and Biobehavioral Reviews·Gabriel S BassiLuis Ulloa
Mar 6, 2021·Brain, Behavior, & Immunity Health·R A NolanP J Gaskill
Jul 2, 2021·Frontiers in Physiology·Xiaoxu YangJingyu Xu

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA

Software Mentioned

GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

© 2022 Meta ULC. All rights reserved