Endotoxin, bacterial, effect

Endotoxin and Muramyl Dipeptide Derivatives. Bacterial cell wall constituents such as the Hpopolysaccharide endotoxin and muramyl dipeptide, which stimulate host defense systems, show radioprotective activity in animals (204). Although endotoxin is most effective when given - 24 h before irradiation, it provides some protection when adrninistered shortiy before and even after radiation exposure. Endotoxin s radioprotective activity is probably related to its Hpid component, and some of its properties may result from PG and leukotriene induction (204). 

Early research showed that Pb exposure could increase sensitivity to bacterially-derived endotoxins [63] as well as increase production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) by macrophages [64-67], Studies in several species indicate that Pb boosts production of TNF-a both immediately following adult exposure and in later life following gestational exposure. Flohe and coworkers [67] reported that Pb-induced elevation in TNF-a production is sensitive to both protein kinase C signaling as well as protein production. Not only can the production of TNF-a be elevated following exposure to Pb, but also the expression of the receptor for TNF-a (TNF-R) is elevated [68], Therefore, the combined effect of elevated cytokine production by macrophages as well as increased receptor expression would be expected to contribute to problematic inflammatory responses. 

LPS, the immunoactive component of endotoxin, is a constituent of the outer membrane of Gram-negative bacterial cell walls. LPS is found in the environment and has been extensively studied, both as a mediator of inflammation and as a major contributing factor to bacterial pathogenesis.60 LPS exerts many of its effects through induction of pro-inflammatory cytokines, including IL-ip, TNF-a and IL-6.61 An important feature... 

Some agents are bifunctional, causing the release of histamine and recruiting leukocytes. Bifunctional mediators include bacterial peptides, endotoxins, DNA, C3a, C5a and bradykinin. Each of these substances can exert dual effects. This may either occur directly, as in the case of bacterial peptides and bradykinin causing chemotaxis and bronchial smooth muscle contraction, or indirectly, as endotoxin and DNA conversion of complement. C3a and C5a act indirectly as complement fragments to effect histamine release, which in turn contracts bronchial smooth muscle. However, both appear to act directly to effect chemotaxis with C5a, the more potent fragment. 

These tests would include compendial tests for Microbial Limits, Sterility, Bacterial Endotoxins, and Antimicrobial Effectiveness. 

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. 

Endotoxin. A heat-stable bacterial toxin not freely liberated into the surrounding medium. Endotoxins are released only when the integrity of the cell wall is disturbed, are less potent than most exotoxins, are less specific, and do not form toxoids. When injected in large quantities, endotoxins produce hemorrhagic shock and severe diarrhea. Smaller amounts cause fever, altered resistance to bacterial infections, leukopenia followed by leukocytosis, and numerous other biological effects. 

The pathogenesis of alcoholic liver disease is a multifactorial process involving metabolic repercussions of ethanol oxidation in the liver, dysregulation of fatty acid oxidation and synthesis, and activation of the innate immune system by a combination of direct effects of ethanol and its metabolites and by bacterial endotoxins that access the liver as a result of ethanol-induced changes in the intestinal tract. Tumor necrosis factor- , a proinflammatory cytokine that is consistently... 

A link between bacteria and tumor therapy was found early, at the beginning of the XVIII century [10]. By the end of the XIX century, Coley [11] developed a treatment for cancer with a mixture of bacterial toxins. In 1943 Shear and Turner [4] found that the antitumor effect of Coley s toxin was due to endotoxins, and after several decades it was shown that the biological activity of LPS was due to the lipid A [5]. We investigated the structures of lipids A with regard to their antitumor activities [12], finding that the optimum in vivo activity is obtained with diglucosamines acylated by 3 long chain fatty acids. 

It was shown that polyglucose splfate could reverse the inhibition, by polymyxin or ribonuclease, of the tumor-damaging effect of endotoxins from Serratia marcescens.m It was also demonstrated that polyglucose sulfate abolishes the ability of lysozyme to lower the fever-producing activity of the bacterial polysaccharide from the same organism. 

Studies in animals clearly indicate that prostaglandins can produce fever when injected into the central nervous system and that Cox-2 induction is responsible for the fever that occurs with bacterial endotoxin and cytokines. To address the potential for an antipyretic effect in humans, Schwartz et al. (1999) administered rofecoxib or ibuprofen to young adults who presented to an infirmary for acute, nonbacterial... 

---