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.
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.
Department of Accident and Emergency, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
Balazs
B
Suto
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.
Istvan
I
Szitter
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12., H-7624 Pécs, Hungary.
Terez
T
Bagoly
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.
Erika
E
Pinter
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.
Janos
J
Szolcsányi
Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
Csaba
C
Loibl
Faculty of Sciences, University of Pécs, Ifjúság u. 6., H-7624 Pécs, Hungary.
Timea
T
Nemeth
Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
Krisztian
K
Tanczos
Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
Tihamer
T
Molnar
Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
Tamas
T
Leiner
Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
Bianka
B
Varnai
Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Pécs, Rákóczi út 2., H-7623 Pécs, Hungary.
Zsofia
Z
Bardonicsek
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.
Zsuzsanna
Z
Helyes
D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D002211:Capsaicin / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010455:Peptides / Q000097:blood* / Q000276:immunology; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D018805:Sepsis / Q000097:blood* / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D019007:P-Selectin; D010455:Peptides; D019010:Vascular Cell Adhesion Molecule-1; C029993:somatostatin-like peptides; D023201:CD40 Ligand; D002211:Capsaicin
Adhesion molecules; Capsaicin-sensitive sensory nerves; Cecum puncture model; Coagulation factors; Cyclo-somatostatin; Cytokines; Radioimmunoassay; Somatostatin; Systemic inflammatory response syndrome