Is there a Place for Monoclonal Antibodies Against Endotoxin in the Therapy of Sepsis?

Eidelman, Leonid A.; Sprung, Charles L.

doi:10.1007/978-3-642-85036-3_24

Cited by 1 publication

(1 citation statement)

References 28 publications

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“…This issue has assumed considerable importance, as evidenced by the controversy that has arisen concerning the results of clinical trials of anti-LPS antibodies for the treatment of sepsis [1,5,7,8,11,12,14,29,32,37,40]. In experimental animals, a single intravenous injection of Gram-negative bacterial LPS has been shown to produce hematological , hemodynamic and metabolic changes close to those observed in patients with sepsis [2,22].…”

Section: Introductionmentioning

confidence: 99%

Influence of human anti-lipopolysaccharide immunoglobulins on tissue distribution and clearance of lipopolysaccharide in rats

Nys¹,

Damas

Damas³

et al. 1999

Med Microbiol Immunol

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To examine the influence of passive immunization on the biological fate of injected lipopolysaccharide (LPS), we used a human IgG preparation (anti-LPS IgG) rich in antibodies to a large panel of smooth and rough purified LPS extracts as well as a normal IgG preparation (standard IgG). Our approach was to compare the uptake of 125I-labeled LPS by the tissues of saline or IgG-treated rats. After intravenous injection, one fraction of 125I-labeled Escherichia coli O55:B5 LPS is rapidly taken up by tissues, while another fraction remained in the blood. Uptake of 125I-labeled LPS was principally observed into the liver and spleen. In rats treated prophylactically with standard IgG, these tissues accumulated significantly larger amount of LPS than the tissues of rats treated with anti-LPS IgG. Nevertheless, both IgG preparations increased the specific binding of LPS by the liver and spleen. High levels of homologous unlabeled LPS decreased the uptake of LPS by the liver, presumably by occupying tissue receptors, whereas in the presence of E. coli O127:B8 LPS, an increase of the uptake of 125I-labeled LPS by the liver and lungs was observed. The pharmacokinetics and tissue distribution of LPS-IgG complexes pre-formed in vitro were compared. In the presence of standard IgG, a unexpected increase of the uptake of LPS by the tissues was recorded, whereas LPS-anti-LPS IgG complexes decreased the binding of 125I-labeled LPS to the tissues. On the other hand, the vascular effects induced by LPS did not appear to be modified in rats pretreated with either IgG preparation. In conclusion, although passive immunization against LPS slightly modified the uptake and clearance of LPS, neither in vitro nor in vivo formation of LPS-anti-LPS IgG complexes afforded a very significant protection against the toxic effects of LPS.

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