Comparable endotoxic properties of lipopolysaccharides are manifest in diverse clinical isolates of gram-negative bacteria

In general there is a poor correlation between serum lipopolysaccharide (LP S; the biologically active constituent of endotoxin) levels and mortality i n septic patients. The objective of this study was to determine if chemical , structural, or biological differences among LPS from different clinical i solates of gram-negative bacteria might explain this discrepancy. LPS prepa rations were made using the hot phenol-water extraction method from eight c linical isolates of gram-negative bacteria. As a percentage of the total we ight of the LPS, the phosphate content ranged from 3.0 to 13.8% (average, 6 .7 +/- 3.6%), and the 2-keto-3-deoxyoctonate content ranged from 1.9 to 27. 4% (average, 8.9 +/- 8.5%). These values were not dissimilar to those obtai ned for a reference endotoxin. In a standard measure of LPS activity, the L imulus amoebocyte lysate assay, there was approximately a twofold differenc e between the least and most active preparations. The two preparations,vith the greatest difference in their ability to elicit the secretion of tumor necrosis factor alpha from a mouse peritoneal macrophage cell line were sim ilar in lethality when administered to mice sensitized to the effects of LP S by D(+)-galactosamine. These relatively minor differences in LPS activity seem unlikely to explain the generally observed discrepancy between serum endotoxin levels and mortality in patients with gram-negative sepsis.