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Endotoxin
Changing Times Endotoxin
E
ndotoxin was described more than 100 years ago, yet scientists are still trying to determine exactly how this lipopolysaccharide produces illness. Endotoxin comes from the outer cell envelope of enteric gram-negative bacteria and is composed of hydrophilic and hydrophobic regions. This molecular structure accounts for the formation of aggregates when endotoxins enter the plasma. Speaking at this year’s North American Veterinary Conference, Dr James N. Moore said, “Endotoxemia is a complicating factor in many diseases affecting horses. Based on data from clinical studies performed at different university hospitals, about 35% of horses presented with colic and 50% of neonatal foals presented with suspected septicemia are endotoxemic. In adult horses, most diseases characterized by endotoxemia affect the gastrointestinal tract (eg, intestinal inflammation or ischemia) or involve bacterial infections affecting the pleural or peritoneal cavities. In neonatal foals, endotoxemia is associated with failure of passive transfer of colostrum.” Only in the last few decades have scientists discovered how the deleterious effects of endotoxins are produced. One by one, various inflammatory mediators that are synthesized and released by mononuclear phagocytes have been described—tumor necrosis factor _, the interleukins, arachidonic acid metabolites, tissue factor, and the like. Recent evidence suggests that endotoxins cause not only the synthesis of pro-inflammatory mediators, but also the synthesis and release of anti-inflammatory mediators such as interleukin 10. Dr Moore explained that under normal circumstances, endotoxins that exist in the lumen of the horse’s
intestine are prevented from gaining access to the general circulation by an efficient mucosal barrier. This barrier is composed of the mucosal epithelial cells themselves, their secretions, and resident bacteria. If this barrier is breached by small numbers of endotoxin molecules, they enter the portal circulation and are removed by mononuclear phagocytes in the liver. In some types of diseases, however, the mucosal barrier is compromised, allowing endotoxins to enter the systemic circulation. This happens commonly with intestinal ischemia or inflammation. Signs of endotoxemia then develop. These include fever, hyperemic or discolored mucous membranes, development of a “toxic line” on the oral mucous membranes, alterations in capillary refill time, decreased gastrointestinal sounds, increased heart and respiratory rates, reduced strength of the arterial pulse, and evidence of dehydration. “Horses with colic that appear to be endotoxemic are candidates for treatment,” said Dr Moore. “While the primary goal should be to identify the underlying cause for endotoxemia, most often treatment must be started before a definitive diagnosis can be made. In these instances, it is reasonable to administer flunixin meglumine and either polymyxin B or anti-endotoxin serum diluted in balanced intravenous fluids. Many clinicians treat horses with pentoxifylline, with the aim being to prevent the development of acute laminitis. Because some of the early effects of endotoxemia can be prevented by nonsteroidal anti-inflammatory drugs or polymyxin B, it is critical that horses receiving these treatments be evaluated closely and that all efforts be expended to determine whether or not the horse has a condition requiring surgical intervention.”
0737-0806/$ - see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2004.11.002
550
Journal of Equine Veterinary Science
December 2004
E
ndotoxin was described more than 100 years ago, yet scientists are still trying to determine exactly how this lipopolysaccharide produces illness. Endotoxin comes from the outer cell envelope of enteric gram-negative bacteria and is composed of hydrophilic and hydrophobic regions. This molecular structure accounts for the formation of aggregates when endotoxins enter the plasma. Speaking at this year’s North American Veterinary Conference, Dr James N. Moore said, “Endotoxemia is a complicating factor in many diseases affecting horses. Based on data from clinical studies performed at different university hospitals, about 35% of horses presented with colic and 50% of neonatal foals presented with suspected septicemia are endotoxemic. In adult horses, most diseases characterized by endotoxemia affect the gastrointestinal tract (eg, intestinal inflammation or ischemia) or involve bacterial infections affecting the pleural or peritoneal cavities. In neonatal foals, endotoxemia is associated with failure of passive transfer of colostrum.” Only in the last few decades have scientists discovered how the deleterious effects of endotoxins are produced. One by one, various inflammatory mediators that are synthesized and released by mononuclear phagocytes have been described—tumor necrosis factor _, the interleukins, arachidonic acid metabolites, tissue factor, and the like. Recent evidence suggests that endotoxins cause not only the synthesis of pro-inflammatory mediators, but also the synthesis and release of anti-inflammatory mediators such as interleukin 10. Dr Moore explained that under normal circumstances, endotoxins that exist in the lumen of the horse’s
intestine are prevented from gaining access to the general circulation by an efficient mucosal barrier. This barrier is composed of the mucosal epithelial cells themselves, their secretions, and resident bacteria. If this barrier is breached by small numbers of endotoxin molecules, they enter the portal circulation and are removed by mononuclear phagocytes in the liver. In some types of diseases, however, the mucosal barrier is compromised, allowing endotoxins to enter the systemic circulation. This happens commonly with intestinal ischemia or inflammation. Signs of endotoxemia then develop. These include fever, hyperemic or discolored mucous membranes, development of a “toxic line” on the oral mucous membranes, alterations in capillary refill time, decreased gastrointestinal sounds, increased heart and respiratory rates, reduced strength of the arterial pulse, and evidence of dehydration. “Horses with colic that appear to be endotoxemic are candidates for treatment,” said Dr Moore. “While the primary goal should be to identify the underlying cause for endotoxemia, most often treatment must be started before a definitive diagnosis can be made. In these instances, it is reasonable to administer flunixin meglumine and either polymyxin B or anti-endotoxin serum diluted in balanced intravenous fluids. Many clinicians treat horses with pentoxifylline, with the aim being to prevent the development of acute laminitis. Because some of the early effects of endotoxemia can be prevented by nonsteroidal anti-inflammatory drugs or polymyxin B, it is critical that horses receiving these treatments be evaluated closely and that all efforts be expended to determine whether or not the horse has a condition requiring surgical intervention.”
0737-0806/$ - see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2004.11.002
550
Journal of Equine Veterinary Science
December 2004