Dopaminergic Control of Inflammation and Glycemia in Sepsis and Diabetes
| Autor: | Eleonora Feketeova, Zhifeng Li, Zoltán Spolarics, Luis Ulloa, Roshan Shah, Biju Joseph |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Blood Glucose Male Fenoldopam medicine.medical_treatment Dopamine Immunology Peritonitis Inflammation Pharmacology dopaminergic agonist Systemic inflammation Diabetes Mellitus Experimental Sepsis 03 medical and health sciences Mice 0302 clinical medicine diabetic sepsis Diabetes mellitus murine sepsis medicine Animals Immunology and Allergy Original Research business.industry Tumor Necrosis Factor-alpha phosphorylation NF-kappa B medicine.disease 3. Good health inflammation mediators Disease Models Animal 030104 developmental biology Cytokine Hyperglycemia Tumor necrosis factor alpha medicine.symptom business lcsh:RC581-607 030217 neurology & neurosurgery Biomarkers Spleen medicine.drug Signal Transduction |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 9 (2018) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.00943 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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