Plasma somatostatin-like immunoreactivity increases in the plasma of septic patients and rats with systemic inflammatory reaction: experimental evidence for its sensory origin and protective role

Peptides. 2014 Apr;54:49-57. doi: 10.1016/j.peptides.2014.01.006. Epub 2014 Jan 20.

Abstract

Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11 systemic inflammatory response syndrome (SIRS) patients were investigated in correlation with cytokines, adhesion molecules and coagulation markers repeatedly during 4 days. The origin and role of SST were studied in the cecum ligation and puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a separate group animals were treated with the somatostatin receptor antagonist cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic patients compared to healthy volunteers during the whole 4-day period. Significantly decreased Horowitz score showed severe lung injury, increased plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin, tissue plasminogen activator and the interleukin 8 and monocyte chemotactic protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly increased in rats both in the plasma and the lung 6h after CLP compared to sham-operation. After RTX pretreatment SST-LI was not altered in intact animals, but the SIRS-induced elevation was absent. Lung MPO activity significantly increased 6h following CLP compared to sham operation, which was significantly higher both after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats survived the 6h, but 60% of the RTX-pretreated ones died showing a significantly worse survival. This is the first comprehensive study in humans and animal experiments providing evidence that SST is released from the activated peptidergic sensory nerves. It gets into the bloodstream and mediates a potent endogenous protective mechanism.

Keywords: Adhesion molecules; Capsaicin-sensitive sensory nerves; Cecum puncture model; Coagulation factors; Cyclo-somatostatin; Cytokines; Radioimmunoassay; Somatostatin; Systemic inflammatory response syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Biomarkers / blood
  • CD40 Ligand / blood
  • Capsaicin / pharmacology
  • Cytokines / blood
  • Disease Models, Animal
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Peptides / blood*
  • Peptides / immunology
  • Rats, Wistar
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism
  • Sepsis / blood*
  • Sepsis / immunology
  • Systemic Inflammatory Response Syndrome / blood*
  • Systemic Inflammatory Response Syndrome / immunology
  • Vascular Cell Adhesion Molecule-1 / blood

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-6
  • P-Selectin
  • Peptides
  • Vascular Cell Adhesion Molecule-1
  • somatostatin-like peptides
  • CD40 Ligand
  • Capsaicin