Targeting endotoxin

The time-line of events in sepsis in both animal models and human sepsis as well as the window for treatments targeting endotoxin are shown in Fig. 15.1. 

Fig. 15.2 Levels of targeting endotoxin (BP binding-protein BPI bactericidal/permeability increasing protein HLF human lactoferrin PMX-HF polymyxin B hemoperfusion)...

Wyckoff, T. J. O., Raetz, C. R. H., and Jackman, J. E. (1998). Anti-bacterial and antiinflammatory agents that target endotoxin. Trends Microbiol. 6, 154- 159. 

One of the most serious consequences of (Gram-negative) bacterial infection is the possible development of septic shock. This is caused by the release of lipopolysaccharide (LPS endotoxin) from the bacterial cell surface. Various anti-LPS monoclonals (mainly targeted at its lipid A component Chapter 3) have been developed. It is hoped that administration of such monoclonals to affected individuals would effectively mop up free LPS, hence ameliorating the severity of the condition. Most trial results to date have proved disappointing in this regard. 

C. Albrecht, D. K. F. Meijer, C. Lebbe, H. Sagesser, B. N. Melgert, K. Poelstra, and J. Reichen, Targeting naproxen coupled to human serum albumin to nonparen-chymal cells reduces endotoxin-induced mortality in rats with biliary cirrhosis, Hepatology 26 1553-1559 (1997). 

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