Biological and Technical Considerations Regarding the Removal of Bacteriotoxins in Sepsis With Emphasis on Toxic Shock Syndrome Toxin 1

Abstract

Severe sepsis is characterized by rapid development of multiple organ failure associated with high mortality. Bacterial toxin release triggers a sequence of events that activates intracellular pathways to produce inflammatory mediators and nitric oxide. There have been numerous attempts to interrupt this devastating cascade by removing toxins, removing or inhibiting mediators, and by blocking receptors of mediators. This review considers toxin properties with a strong focus on toxic shock syndrome toxin 1 and the potential of various removal technologies in relation to these properties. The distribution of toxins in vivo forms a key issue but is nevertheless poorly defined. For toxic shock syndrome toxin 1, either a high clearance or a high degree of compartmentalization to a space not accessible by pheresis or immunoabsorption technologies seems likely. Attempts to remove toxins to treat sepsis may appear futile if we cannot access this space or when the level of induced clearance is too low compared with natural clearance. The impact of these considerations is highly dependent on the exact toxin biology in vivo. Extrapolated to other toxins, we indicate a set of general requirements to be met to facilitate successful toxin removal by a pheresis technique.

Fructose-coated Ångstrom silver prevents sepsis by killing bacteria and attenuating bacterial toxin-induced injuries

“…Sepsis is a highly lethal condition characterized by systemic inflammation, resulting from uncontrolled host immune responses to a serious infection 5 . The strong activation of whole-body inflammation is essential for preventing against the invading pathogens, but may cause detrimental consequences such as multiple-organ failure 52 , 53 . As the major members of the innate immune system, neutrophils, and macrophages recognize the microbial components such as the bacterial LPS and participate in the clearance of microbes during sepsis 54 .…”

Nitric oxide production contributes toBacillus anthracisedema toxin-associated arterial hypotension and lethality: ex vivo and in vivo studies in the rat

“…These findings suggested that ET's inhibition of arterial contractile function might be mediated in part by release of an endothelial derived relaxant factor (EDRF). Nitric oxide (NO) is a potent EDRF, which has been associated with the pathogenic effects of several bacterial toxins (4,6,37). Therefore, using both an ex vivo rat aortic ring model and an in vivo rat model, in combination with three nitric oxide synthase (NOS) inhibitors with the potential to inhibit one or more of the three NOS isoforms [endothelial (eNOS), neuronal (nNOS), and inducible (iNOS)], we tested the hypothesis that NO production contributes to ET's hypotensive and lethal effects.…”