Anti-endotoxin antibody

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. 

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... 

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. 

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. 

In chimpanzees, administration of Fab fragments of a monoclonal anti-F-VII antibody preceding an endotoxin bolus injection effectively blocked the activation of the coagulation pathway (B25). Administration of monoclonal anti-lL-6 under the same experimental conditions attenuated the activation of coagulation, while the fibrinolytic system remained unaltered. However, administration of monoclonal anti-TNF enhanced the tendency to microvascular thrombosis (P17,18). Monoclonal anti-TF antibodies administered to baboons as a pretreatment attenuated coagulopathy after induction of E. coli sepsis in these animals (T4). Primates pretreated with anti-C5a antibodies before infusion of E. coli developed less hypotension and had better survival rates than untreated animals, who developed ARDS and septic shock with a mortality rate of 75% (S35, Z6). No favorable treatment results have been published yet with one of these treatment modalities given to humans. 

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

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. 

Note. ELISA = enzyme-linked immunosorbent assay, FACS = fluorescence-activated cell sorting, HPLC = high-performance liquid chromatography, IHC = immunohistochemistry, LC/MS = liquid chromatography/MS = mass spectrometry, LPS = lipopolysaccharide (endotoxin), NA = not applicable, PAHA = (nonhuman) primate anti-human antibodies. 

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

There are other ways in which endotoxins may act to produce cotton dust induced airway disease. These include 1) an instrinsic toxicity due to lipid A, responsible for both pyro-genicity and tissue damage 2) a hypersensitivity reaction involving anti-lipid A antibodies. Further, changes in mechanical properties of the lung could be explained by the release of histamine or serotonin caused by endotoxins. 

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