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Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis.
Abstract: Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macrophages become highly activated for enhanced secretory, phagocytic and cidal functions by LPS. Macrophage-derived cytokines are responsible for many of the pathophysiologic consequences of endotoxemia. The arachidonic acid metabolites, prostacyclin and thromboxane A2 likely mediate early hemodynamic dysfunction and the leukotrienes may potentiate tissue ischemia during endotoxemia. Interleukin 1 (IL-1) induces fever and is responsible for the inflammatory cascade, which constitutes the acute phase response. Tumor necrosis factor (TNF), an important proximal mediator of the effects of LPS, acts to initiate events and formation of other molecules that affect shock and tissue injury. Systemic administration of TNF produces most of the physiologic derangements that are associated with endotoxemia and antibodies that are directed against TNF significantly reduce LPS-induced mortality in experimental animals. In response to endotoxins, mononuclear phagocytes express thromboplastin-like procoagulant activity (PCA), which initiates microvascular thrombosis. Both IL-1 and TNF induce PCA expression, creating a positive feedback loop for LPS-induced coagulopathy. A macrophage-derived platelet activating factor contributes to coagulation dysfunction and further stimulates arachidonic acid metabolism. The ultimate consequences of endotoxemia are multiple system organ failure and death. The numerous feedback loops and intertwining cascades of mediators during endotoxemia defy simplistic methods of treatment. The optimal therapy likely involves methods to alter the generation of inflammatory mediators by mononuclear phagocytes.
Publication Date: 1991-05-01 PubMed ID: 1920254DOI: 10.1111/j.1939-1676.1991.tb00944.xGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Review
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The study focuses on the causes and processes involved in endotoxemia – a fatal condition in horses closely linked to gastrointestinal issues. The disease arises when endotoxins, normally confined within the bowel, enter the bloodstream due to damaged mucous membranes or proliferation of certain bacteria in tissues.
Key elements in endotoxemia
- The movement of endotoxins from the bowel to the bloodstream plays a crucial role in endotoxemia. This primarily occurs in two ways: either through a damaged intestinal mucosa or due to rapid growth of gram-negative organisms in the tissues.
- Mononuclear phagocytes are responsible for clearing endotoxins from the bloodstream. They respond to lipopolysaccharides (LPS) present on endotoxins, and this reaction significantly determines the severity of the disease. More specifically, macrophages within these phagocyte cells become more activated by the LPS, enhancing their secretory, phagocytic, and cidal functions.
Role of cytokines and metabolites
- The article highlights that macrophage-derived cytokines are accountable for many of the pathophysiological outcomes of endotoxemia. Two such cytokines are Interleukin 1 (IL-1) and Tumor Necrosis Factor (TNF).
- IL-1 is involved in inducing fever and triggering the inflammatory cascade, which embodies the initial negative response in endotoxemia.
- TNF, another important component in response to LPS, helps initiate various events and formation of other molecules affecting shock and tissue injury. It is noteworthy that the administration of TNF alone can lead to physiological disturbances associated with endotoxemia and their antibodies significantly reduce LPS-induced mortality in experimental animals.
- Endotoxins also stimulate mononuclear phagocytes to express Procoagulant Activity (PCA), contributing to microvascular thrombosis.
Feedback loop and potential remedies
- Both IL-1 and TNF induce PCA expression, thus creating a feedback loop for LPS-induced clotting disorders. This, in turn, contributes to coagulation dysfunction and further induces metabolism of the fatty acid, arachidonic acid.
- The possible treatments for this complex condition likely involve methods to tweak the generation of inflammatory mediators by mononuclear phagocytes. However, the highly interlinked mediator cascades and feedback systems during endotoxemia resist straightforward treatment tactics.
In conclusion, this research article gives a comprehensive view of the multifaceted process of endotoxemia in horses, the significance of various cellular reactions, and a direction for potential approaches in managing this condition.
Cite This Article
APA
Morris DD.
(1991).
Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis.
J Vet Intern Med, 5(3), 167-181.
https://doi.org/10.1111/j.1939-1676.1991.tb00944.x Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
MeSH Terms
- Animals
- Endotoxins / poisoning
- Gram-Negative Bacterial Infections / etiology
- Gram-Negative Bacterial Infections / veterinary
- Horse Diseases / chemically induced
- Horses
Citations
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