Somatostatin reduces the levels of tumor necrosis factor alpha in a rat model of endotoxemia induced bylipopolysaccharide

Abstract

The role of tumor necrosis factor alpha (TNF) in the toxic and lethal effects of the endotoxemia associated with septic shock is well known. This study was designed to establish whether natural somatostatin (SS-14) is capable of modifying the production of TNF in a model of septic shock induced in the rat by bacterial lipopolysaccharide (LPS), and its theoretical relationship to prostaglandin E2 (PGE2). An experimental study was carried out in 80 Wistar rats subjected to intravenous LPS injection. Perfusion of SS-14 at 2 micrograms/h or continuous isotonic saline (IS) at 0.1 ml/h started 30 min prior to LPS injection and continued until 90 min after. All the animals were primed 15 days earlier with on intraperitoneal dose of BCG (2.2 x 10(7) CFU). ELISA assays were used to measure TNF levels after 90 min of perfusion and those of PGE2 at 30 and 90 min. The effects of two different doses of LPS (0.5 mg/kg of body weight and 5 mg/kg bw) were compared. SS-14 administration was associated with a decrease in TNF levels (1130.0 +/- 272.4 vs 4720.0 +/- 1278.1 pg/ml, P = 0.013), and an increase in serum PGE2 basally (255.7 +/- 94.2 vs 62.0 +/- 10.6 pg/ml, P = 0.04) and after 90 min of perfusion (1872.7 +/- 1250.6 vs 1009.7 +/- 612.0 pg/ml, P = NS), there being a statistically significant correlation between the basal PGE2 levels and these TNF after 90 min when compared using a regression model (r = -0.88, P = 0.04 for the 0.5 mg/kg dose; r = -0.47, P = 0.07 for 5 mg/kg). At 90 min, the level of TNF also depended on the PGE2 values (r = 0.84, P = 0.07 for 0.5 mg/kg; r = 0.55, P = 0.03 for 5 mg/kg). Multiple regression permitted TNF levels to be estimated on the basis of basal and 90 min PGE2 levels (P = 0.03). Pretreatment with SS-14 led to a significant reduction of TNF and an increase of PGE2, there being an apparent correlation between the two.

Inhibition of infection‐mediated preterm birth by administration of broad spectrum chemokine inhibitor in mice

“…In our study, we showed that not only TNF‐α, but also IL‐6, Csf2 ( P < 0.001) and IL‐1b ( P = 0.07) protein expression was inhibited by BSCI in maternal plasma after low‐dose systemic LPS administration. Similarly, natural somatostatin (SS‐14) has been shown to be capable of modifying TNF‐α secretion in a rat model of septic shock induced by bacterial LPS . Cortistatin, novel somatostatin‐related cyclic neuropeptide, down‐regulated the production of inflammatory mediators by LPS‐activated macrophages .…”

Preventive Effect of SA13353, a Novel Transient Receptor Potential Vanilloid 1 Agonist, on Ischemia/Reperfusion-Induced Renal Injury in Rats

“…On the other hand, SA13353 further enhanced the increases in IL-10 mRNA and its serum protein levels elicited by the ischemia/reperfusion. Previous studies have demonstrated that neuropeptides such as CGRP [33][34][35] and somatostatin [36] inhibited the LPS-induced TNF-α production in vivo and in vitro. We also found recently that orally administered SA13353 evoked the release of CGRP and somatostatin [22].…”

Systemic Chemical Desensitization of Peptidergic Sensory Neurons with Resiniferatoxin Inhibits Experimental Periodontitis

“…Substance P is known to be a potent vasodilator, increasing vascular permeability and stimulating many pro-inflammatory processes, including LPS-induced TNF-α production and release [ 49 , 50 ]. Calcitonin gene-related peptide and somatostatin, on the other hand, inhibit TNF-α [ 51 - 53 ]. In our in vivo study, the RTX-treated animals reacted towards a stronger TNF-α response to systemic LPS stimulation.…”