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 septi c shock induced in the rat by bacterial lipopolysaccharide (LPS), and its theoretical relationship to prostaglandin E(2) (PGE(2)). An experi mental study was carried out in 80 Wistar rats subjected to intravenou s 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 con tinued until 90 min after. All the animals were primed 15 days earlier with on intraperitoneal dose of BCG (2.2x10(7) CFU). ELISA assays wer e used to measure TNF levels after 90 min of perfusion and those of PG E(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 administrati on was associated with a decrease in TNF levels (1130.0+/-272.4 vs 472 0.0+/-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 perfus ion (1872.7+/-1250.6 vs 1009.7+/-612.0 pg/ml, P=NS), there being a sta tistically significant correlation between the basal PGE(2) levels and these TNF after 90 min when compared using a regression model (r=-0.8 8, 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 per mitted 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 reduct ion of TNF and an increase of PGE(2), there being an apparent correlat ion between the two.