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

Balazs Suto; Istvan Szitter; Terez Bagoly; Erika Pinter; Janos Szolcsányi; Csaba Loibl; Timea Nemeth; Krisztian Tanczos; Tihamer Molnar; Tamas Leiner; Bianka Varnai; Zsofia Bardonicsek; Zsuzsanna Helyes

doi:10.1016/j.peptides.2014.01.006

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.

Authors

Affiliations

¹ Department of Accident and Emergency, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
² Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, Ifjúság u. 20., H-7624 Pécs, Hungary.
³ Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary.
⁴ Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, Ifjúság u. 20., H-7624 Pécs, Hungary; PharmInVivo Ltd., Szondi Gy. u. 10., H-7629 Pécs, Hungary.
⁵ Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
⁶ Faculty of Sciences, University of Pécs, Ifjúság u. 6., H-7624 Pécs, Hungary.
⁷ Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, Ifjúság u. 20., H-7624 Pécs, Hungary; PharmInVivo Ltd., Szondi Gy. u. 10., H-7629 Pécs, Hungary. Electronic address: zsuzsanna.helyes@aok.pte.hu.

PMID: 24457113
DOI: 10.1016/j.peptides.2014.01.006

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