Characterization of the pyrogenicity of two different lipopolysaccharides and their lipid A-bovine serum albumin complexes.

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Abstract
In order to elucidate the dependency of pyrogenicity of lipopolysaccharide (LPS) on the lipid A structure, we investigated the pyrogenicity of both LPS and lipid A prepared from Mima polymorpha var. oxidans which is deficient in 3-hydroxymyristic acids linked to the 3-hydroxy group of other fatty acids. LPS and lipid A were also prepared as reference compounds from Escherichia coli UKT-B. Furthermore, the establishment of reliable indices for pyrogenicity was undertaken. The following results were obtained. 1) The correlation in linearity was demonstrated between maximal increase in body temperature (.DELTA.Tmax) and dose of LPS or lipid A complexed with bovine serum albumin (BSA). The dose-response curves based on .DELTA.Tmax were more reliable statistically than the Fever Index-4h representing the area under fever curves for 4 h. 2) The minimum pyrogenic dose (MPD) of E. coli LPS was 1.6 .times. 10-3 .mu.g/kg i.v. In contrast, the MPD of M. polymorpha LPS was 7.0 .times. 10-3 .mu.g/kg i.v. By intracisternal injection, the MPD of E. coli LPS was 2.5 .times. 10-6 .mu.g/kg and that of M. polymorpha LPS 1.0 .times. 10-4 .mu.g/kg. 3) The end points of Limulus amoebocyte lysate gelation were 10-5 .mu.g/ml in E. coli LPS and 10-3 .mu.g/ml in M. polymorpha LPS. 4) The MPDs of lipid A/BSA complexes by i.v. injection were 0.15 .mu.g/kg in E. coli and 2.5 .mu.g/kg in M. polymorphia. 5) The rabbits immunized with E. coli lipid A/BSA complex acquired pyrogenic tolerance to the parent LPS but the cross tolerance to M. polymorpha LPS was not observed. These results indicated that certain differences in lipid A structure may be dominant factors for LPS-induced fever. However, it was suggested that the polysaccharide regions of a LPS molecule may also play an important role in LPS-induced fever.

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