CORRELATIONS BETWEEN ENDOTOXIN, INTERFERON-GAMMA, BIOPTERIN AND SERUMPHOSPHOLIPASE A(2)-ACTIVITIES DURING LETHAL GRAM-NEGATIVE SEPSIS IN RATS

Objective: To establish a standardised reproducible animal model of in traperitoneal sepsis, and to investigate early immunoserological respo nses to find a mediator-based system for evaluation and grading of dif fuse peritonitis in patients. Design: Prospective experimental study. Setting: 4 Teaching hospitals, Germany and Austria. Material: 42 LEW. 1W rats, 12 of which acted as controls. Interventions: Gram negative s epsis was induced by intraperitoneal injection of 6ml of a mixture of Escherichia coli (K1:H+) 10(10) organisms/ml, autogenous haemoglobin 2 .9 ml (haemoglobin concentration 3%): 0.9% sodium chloride 3 ml, and s uspension 0.1 ml. Control rats were given physiological saline 6 ml al one. Main outcome measures: Concentrations of endotoxin, interferon ga mma (IFN-gamma), and biopterin, and serum phospholipase A(2) (PLA(2)) activity. Results: There were significant differences between the sept ic and control rats in concentrations of endotoxin (EU/ml) (median (in terquartile range) 21.85 (2.02-159.5) compared with 0, p < 0.0001; IFN -gamma (pg/ml) 1263.0 (271.0-7575.0) compared with 101.0 (89.0-141.0), p < 0.0001; biopterin (nmol/L) 111.0 (66.4-156.3) compared with 53.7 (38.3-67.6), p < 0.001; and PLA(2) (U/L) 163.0 (125.8-209.0) compared with 112.5 (88.5-126.5) p < 0.01. Conclusions: Measurements of concent rations of endotoxin, IFN-gamma, pteridines, and PLA(2) activity may w ell be adequate markers for early recognition of sepsis, and perhaps f or grading it during the first 6 hours after induction. The allow a cl ear distinction to be made between septic and non-septic disorders in 87% of cases.