Dopaminergic control of inflammation and glycemia in sepsis and diabetes

Eleonora Feketeova, Zhifeng Li, Biju Joseph, Roshan Shah, Zoltan Spolarics, Luis Ulloa

Research output: Contribution to journalArticle

2 Citations (Scopus)

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-κB phosphorylation. Fenoldopam inhibits TNF production in splenocytes even at high glucose concentrations and inhibits the canonical NF-κB pathway by inhibiting p65RelA and p50NF-κB1 phosphorylation without affecting the non-canonical NF-κB proteins. Treatment with fenoldopam rescues diabetic mice from established polymicrobial peritonitis even when the treatment is started after the onset of sepsis. These results suggest that dopaminergic agonists can control hyperglycemia, systemic inflammation and provide therapeutic advantages for treating diabetic patients with sepsis in a clinically relevant time frame.

Original languageEnglish (US)
Article number943
JournalFrontiers in immunology
Volume9
Issue numberMAY
DOIs
StatePublished - May 4 2018

Fingerprint

Sepsis
Inflammation
Fenoldopam
Hyperglycemia
Tumor Necrosis Factor-alpha
Dopamine Agonists
Phosphorylation
Therapeutics
Glucose
Mortality
Peritonitis
Serum
Anti-Inflammatory Agents
Theoretical Models
Clinical Trials
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • Diabetic sepsis
  • Dopaminergic agonist
  • Inflammation mediators
  • Murine sepsis
  • Phosphorylation

Cite this

Feketeova, Eleonora ; Li, Zhifeng ; Joseph, Biju ; Shah, Roshan ; Spolarics, Zoltan ; Ulloa, Luis. / Dopaminergic control of inflammation and glycemia in sepsis and diabetes. In: Frontiers in immunology. 2018 ; Vol. 9, No. MAY.
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Dopaminergic control of inflammation and glycemia in sepsis and diabetes. / Feketeova, Eleonora; Li, Zhifeng; Joseph, Biju; Shah, Roshan; Spolarics, Zoltan; Ulloa, Luis.

In: Frontiers in immunology, Vol. 9, No. MAY, 943, 04.05.2018.

Research output: Contribution to journalArticle

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AU - Li, Zhifeng

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AU - Shah, Roshan

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AU - Ulloa, Luis

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