Artikel
Increased hepatic LBP aggravated LPS-induced inflammatory response after 70% partial hepatectomy
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Veröffentlicht: | 20. Mai 2011 |
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Introduction: Liver failure associated with LPS translocation represents a major risk to develop SIRS and sepsis after PH. The inflammatory response to LPS is dependent on binding of LPS/LBP complex to TLR4. Serum LBP was recently discovered as a candidate biomarker for the diagnosis of sepsis. However, the correlation of serum LBP with disease severity and outcome is weak. We hypothesized that the intensity of the inflammatory response after partial hepatectomy is related to both high systemic LPS and hepatic LBP levels.
Materials and methods: LPS levels were increased by partial hepatectomy (slight increase), LPS-injection (moderate increase) or by adding both stimuli (strong increase). LBP expression was induced in naïve and liver resected rats by G-CSF pretreatment.
We compared LBP-levels and the inflammatory response after PH in rats treated with LPS or/and G-CSF in comparison to non-operated rats. Serum and hepatic LBP levels were quantified using Western Blot and/or qPCR. Mortality, hepatic injury (AST, ALT), hepatic neutrophil infiltration, and proinflammatory cytokines (TNF-a, IL-6) were described as parameters reflecting damage and inflammatory response.
Results: LPS, G-CSF and combined treatment induced a 2-fold increase in serum LBP levels in naïve and liver resected rats. In contrast, hepatic LBP mRNA and protein levels were increased slightly after GCSF-pretreatment, but up to 30-fold after LPS injection and even more in G-CSF LPS group. The intensity of the inflammatory damage and cytokine response (liver enzyme levels, systemic cytokine levels) paralleled hepatic LBP levels. Maximal induction of hepatic LBP-expression via GCSF-pretreatment prior to inflammatory activation via LPS-injection and eventually PH caused an overwhelming lethal systemic inflammatory response syndrome.
Conclusion: The intensity of the postoperative systemic inflammatory response seemed to be related to the systemic LPS-levels and to the hepatic LBP-levels. Compared with serum LBP levels, determination of hepatic LBP may be more predictive of the severity and outcome in patients with sepsis.