Mechanism of hepatocellular dysfunction during sepsis: the role of gut-derived norepinephrine (review).

  • Authors:
    • D J Koo
    • I H Chaudry
    • P Wang
  • View Affiliations

  • Published online on: May 1, 2000     https://doi.org/10.3892/ijmm.5.5.457
  • Pages: 457-522
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Abstract

Despite major advances in the management of trauma victims, the incidence of sepsis has increased significantly over the past two decades. The increasingly high morbidity and mortality associated with sepsis could be attributed to the fact that early alterations of cellular functions are not recognized, thereby leading to delayed or inadequate treatment of the septic patient. In this regard, studies have demonstrated that hepatocellular function is depressed early after the onset of sepsis. Due to its major role in metabolism and host defense mechanisms, it is becoming increasingly evident that the liver is an important organ in the development of multiple organ dysfunction during sepsis. Mediators which are released from the gut have been implicated in initiating hepatocellular dysfunction via the release of inflammatory cytokines such as TNF-alpha by Kupffer cells, the resident macrophages present in the hepatic sinusoids. Kupffer cells, by virtue of their location in the mainstream of splanchnic blood flow, are positioned to receive a constant exposure to gut-derived mediators known to activate macrophages. In this review article, we will first describe the animal model of cecal ligation and puncture which has led to our understanding of the consequences of sepsis. We will then discuss the occurrence of hepatocellular dysfunction during early sepsis. The mechanism responsible for such a deleterious alteration in organ function, focusing especially on the role of gut-derived norepinephrine and its effect on TNF-alpha release by Kupffer cells, will be specifically discussed. Moreover, we will discuss potential approaches for modulating Kupffer cell inflammatory cytokine release and improving hepatocellular function during sepsis.

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May 2000
Volume 5 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Koo D, Chaudry I and Wang P: Mechanism of hepatocellular dysfunction during sepsis: the role of gut-derived norepinephrine (review).. Int J Mol Med 5: 457-522, 2000
APA
Koo, D., Chaudry, I., & Wang, P. (2000). Mechanism of hepatocellular dysfunction during sepsis: the role of gut-derived norepinephrine (review).. International Journal of Molecular Medicine, 5, 457-522. https://doi.org/10.3892/ijmm.5.5.457
MLA
Koo, D., Chaudry, I., Wang, P."Mechanism of hepatocellular dysfunction during sepsis: the role of gut-derived norepinephrine (review).". International Journal of Molecular Medicine 5.5 (2000): 457-522.
Chicago
Koo, D., Chaudry, I., Wang, P."Mechanism of hepatocellular dysfunction during sepsis: the role of gut-derived norepinephrine (review).". International Journal of Molecular Medicine 5, no. 5 (2000): 457-522. https://doi.org/10.3892/ijmm.5.5.457