SOMATOSTATIN REDUCES THE LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA IN A RAT MODEL OF ENDOTOXEMIA INDUCED BY LIPOPOLYSACCHARIDE

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 E(2) (PGE(2)). An experimental study was carried out in 80 Wistar rats subjected to intravenous LPS injection. Perfusion of SS-14 at 2 mu g/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 (2.2x10(7) CFU). ELISA assays were used to measure TNF levels after 90 min of perfusion and those of PGE(2) 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 PGE(2) 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 PGE(2) 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 PGE(2) 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 PGE, levels (P=0.03). Pretreatment with SS-14 led to a significant reduction of TNF and an increase of PGE(2), there being an apparent correlation between the two.