Elsevier

Journal of Hepatology

Volume 23, Issue 4, October 1995, Pages 391-395
Journal of Hepatology

Plasma endotoxin and tumor necrosis factor-α in the hyperkinetic state of cirrhosis

https://doi.org/10.1016/0168-8278(95)80196-0Get rights and content

Abstract

Background/Aims: The factors which trigger the hyperdynamic circulation in cirrhosis remain poorly defined. Plasma levels of the potent vasodilators endotoxin and tumor necrosis factor-α may be elevated in patients with cirrhosis, and therefore the potential role of these substances was assessed in the hyperkinetic circulation in cirrhosis.

Methods: Forty-nine patients in stable condition underwent systemic and hepatic hemodynamic measurements, and right atrial blood sampling for endotoxin and tumor necrosis factor-α assays. Patients were divided into three groups according to the severity of the disease: group 1 consisted of eight patients with normal liver or mild hepatic fibrosis, and groups 2 and 3 contained 17 and 24 patients with Child A and Child B or C cirrhosis, respectively.

Results: Systemic vascular resistance decreased and cardiac index increased from group 1 to 3: 1530±196 dyn·s·cm−5 to 990±72 dyn·s·cm−5 (mea±S.E.; p<0.05) and 3.1±0.3 l·min−1·min−2 to 4.2−0.2 l·min−1·m−2, respectively. Endotoxin was not detectable in any of the groups and tumor necrosis factor-α was increased in one patient from group 1, six from group 2 and six from group 3. Mean tumor necrosis factor-α levels were not different among the groups (10±5, 18±5 and 17±7 pg/ml in groups 1, 2 and 3, respectively). Systemic vascular resistance and cardiac index were not correlated to plasma tumor necrosis factor-α levels; patients with increased levels of this cytokine did not have worse hyperdynamic circulation in any of the groups.

Conclusions: These results suggest that tumor necrosis factor-α and endotoxin do not play a role in the maintenance of the hyperkinetic state of cirrhosis.

References (29)

  • JN Benoit et al.

    Role of glucagon in splanchnic hyperemia of chronic portal hypertension

    Am J Physiol

    (1986)
  • JM Pak et al.

    Vasoactive effects of bile salts in cirrhotic rats: in vivo and in vitro studies

    Hepatology

    (1993)
  • F Oberti et al.

    Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension

    Hepatology

    (1993)
  • HR Michie et al.

    Detection of circulating tumor necrosis factor after endotoxin administration

    N Engl J Med

    (1988)
  • Cited by (26)

    • Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis

      2016, Journal of Critical Care
      Citation Excerpt :

      Albumin also binds arachidonic acid, prostaglandins, thromboxane, and leukotrienes and has a dichotomous effect on eicosanoids. On the one hand, the protein, which has intrinsic enzymatic activity, catalyzes their synthesis or degradation, whereas on the other hand, it stabilizes the molecule by delaying hydrolysis [47–52]. Therefore, albumin serves to store, transport, and provide NO and eicosanoids to target sites, thus acting as a protective agent to mitigate harmful biological effects.

    • Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance

      2014, Journal of Hepatology
      Citation Excerpt :

      As shown in Table 1, the in vivo activation of circulating immune cells in cirrhosis is supported by the presence of: (i) neutrophils, showing an increased respiratory burst and enhanced expression of CD11b [27,31], (ii) monocytes, featuring the enhanced surface expression of HLA-DR and activation/co-stimulatory molecules CD80 and CD86, as well as the upregulation of pathways and the increased production of pro-inflammatory cytokines (e.g. TNFα, IL-6) [34,50,52,57,58], (iii) T lymphocytes, showing an increased surface expression of activation antigens that are polarized to augmented IFNγ, TNFα, and IL-17 production [34,50,59,60], and (iv) B lymphocytes, showing an upregulation of the activation/co-stimulatory markers, HLA-DR and CD86, and an increased responsiveness to cytokines and hyperglobulinemia [61,62]. Activated circulating immune cells eventually become major contributors to increased serum concentrations of pro-inflammatory cytokines such as TNFα, TNFα soluble receptors I and II, IL-1β, IL-6 and IFNγ, IL-17, as well as ICAM-1 and VCAM-1, present in experimental and human cirrhosis [34,50,59,63–81]. Specifically, monocytes are a major source of circulating TNFα in cirrhosis, as shown by the direct correlation observed between serum levels of this critical effector cytokine and the TNFα production capacity of monocytes [34].

    • Human serum albumin, systemic inflammation, and cirrhosis

      2014, Journal of Hepatology
      Citation Excerpt :

      The first is multi-organ dysfunction. The second is a systemic inflammatory reaction with increased plasma and ascitic fluid concentration of cytokines and C-reactive protein (CRP) [121–129]. Finally, the third is an increased systemic oxidative stress with a high levels of oxidized HSA and of other markers of oxidative stress [58,72].

    View all citing articles on Scopus
    View full text