Anti-endotoxin

Lynn, W.A. Anti-endotoxin therapeutic options for the treatment of sepsis. J Antimicrob Chemother 41 Suppl A, (1998) 71-80. 

David, S.A. Towards a rational development of anti-endotoxin agents novel approaches to sequestration of bacterial endotoxins with small molecules. J Molec Recognit 14 (2001) 370-387. 

Ziegler, E.J., Smith, C.R. Anti-endotoxin monoclonal antibodies. N Engl J Med 326 (1992) 1165. 

Despite both the directness and simplicity of the hypothesis, namely that antibody directed toward a common, toxic moiety of endotoxin has therapeutic potential, the concept of anti-endotoxin antibody has been difficult to prove and mired in controversy. 

Non-vaccine generated anti-endotoxin reagents that bind and/or neutralize LPS, such as bactericidal permeability increasing protein (BPI), endotoxin neutralizing protein (ENP), and cationic peptide 18 conjugated to immunoglobulin G (CAP 18-IgG) have been developed for the adjunctive therapy of sepsis, but only BPI has progressed to clinical trials (Levin et al., 2000). 

Given that anti-endotoxin antibodies may provide benefit under various clinical conditions, we prepared a subunit LPS vaccine from the J5 mutant. Previous experience with whole, killed Gram negative bacterial vaccines (e.g. typhoid, cholera and Salmonella Re vaccines) demonstrated a high degree of reactogenicity... 

Immunization Strategies with Anti-Endotoxin Vaccines... 

Other Potential Applications of Anti-Endotoxin Vaccine... 

Lugowski, C., Niedziela, T., Jachymek, W. Anti-endotoxin antibodies directed against Escherichia coli Rl oligosaccharide core-tetanus toxoid conjugate bind to smooth live bacteria and smooth lipopolysaccharides and attenuate their tumor necrosis factor stimulating activity, FEMS Immunol Med Microbiol 16 (1996b) 31-38. 

Lugowski, C., Czaja, J., Jachymek, W., Niedziela, T. Lakomska, J. Serological characterization of anti-endotoxin serum directed against the conjugate of oligosaccharide core of Escherichia coli type R4 with tetanus toxoid. J Endotoxin Res 6 (2000) 166 (Abstr). 

Elsbach, P., Weiss, J., Doerfler, M., Shu, C., Kohn, F., Ammons, W.S., Kung, A.H., Meszaros, K.K., Parent, J.B. The bactericidal/permeability increasing protein of neutrophils is a potent antibacterial and anti-endotoxin agent in vitro and in vivo. Prog Clin Biol Res 388 (1994) 41-51. 

Romulo, R.L., Palardy, J.E., Opal, S.M. Efficacy of anti-endotoxin monoclonal antibody E5 alone or in combination with ciprofloxacin in neutropenic rats with Pseudomonas sepsis. J Infect Dis 167 (1993) 126-130. 

The gold standard for anti-endotoxin peptides is Polymyxin B (PMB), a small cyclic lipopep-tide (O Fig. 17). It neutralizes LPS very efficiently, and has been shown to employ a two-step binding process where it first attaches to the LPS by electrostatic interactions and then inserts its acyl chain into the lipid layer. PMB is used only topically because it is neurotoxic. However, there have been many attempts to design analogs with lower toxicity [245,246,247]. Synthetic anti-endotoxin peptides (SAEP) based on Polymyxin B have been engineered to have low toxicity while retaining the in vitro and in vivo detoxification ability of PMB. Furthermore,... 

Rietschel ET, Cavaillon JM. 2002. Endotoxin and anti-endotoxin. The contribution of the schools of Koch and Pasteur life, milestone-experiments and concepts of Richard Pfeiffer (Berlin) and Alexan-... 

Wenzel, R., Anti-endotoxin monoclonal antibodies - a second look. N. Engl. J. Med. 1992, 326, 1151-1153. 

Mihas A A, Ceballos R, Mihas TA, Hirshowitz BI (1990) Modification of the hepatotoxic-ity of D-galactosamine in the rat by an anti-endotoxin. J Med 21 301-311 Miyai K, Slusser RJ, Ruebner BH (1962) Viral hepatitis in mice an electron microscopic study. Exp Mol Pathol 2 464-480... 

Rogy MA, Moldawer LL, Oldenburg HS, Thompson WA, Montegut WJ, Stackpole SA, Kumar A, Pulladino MA, Maria MN, Lowry SE, Anti-endotoxin therapy in primate bacteremia with HA-1 A and BPl. Ann Surg 1994 220 77-85. 

Gough MA, Hancock REW, Kelly NM. Anti-endotoxin activity of cationic peptide antibiotics. Infect immun 1996 64 4922-4927. 

Fomsgaard, A., Neilsen, R., Froberg, K.D., Back, L., and Deghn, H.K. 1987. Endotoxinaemia in toxic shock syndrome treated with anti-endotoxin antibodies. Lancet 1 514-515. 

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