ENDOTOXIN CONCENTRATION BY LIMULUS ASSAY CORRELATES WITH BIOLOGICAL-ACTIVITY IN MICE AND HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Endotoxin is thought to play a major role in septic shock and multiple systemic organ failure (MOF). However, endotoxin is not always detect ed in the plasma during Gram-negative sepsis by current Limulus lysate assays. Additionally, it is unknown to what extent the biological act ivity of endotoxin is truly reflected in endotoxemia. This paper asses ses quantitatively a comparison of three types of Limulus assays for t he detection of the biological activity of endotoxin in plasma. Mouse lethal activity and TNF production were used for assessment of the bio logical activity of endotoxin both before and after potential modifica tion of LPS activity by plasma constituents. We have concluded that th e dilution and heating method coupled with a toxinometer provides the most accurate correlation with other biological activities of endotoxi n in plasma. The fact that the biological activity of endotoxin decrea sed to 17% of initial dose after incubation at 37 degrees C for 90 min in normal plasma suggests further a temporal dependence of time in pl asma upon the manifestation of biological activities normally attribut able to this biologically active microbial constituent found in the pl asma of septic patients.