Effect of growth factors as therapeutic drugs on hepatic metabolism during the systemic inflammatory response syndrome

Marc G. Jeschke, David Herndon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Characteristic for critically ill patients is a hypermetabolism and catabolism that is associated with impairment of the structure and function of essential organs, such as the immune system, kidney, peripheral muscles and the liver. The liver-gut-axis, with liver integrity, metabolism and function are crucial for survival of patients suffering from trauma, operations or infections. The hepatic acute phase response represents a cascade of events characterized by the upregulation of acute phase proteins and the downregulation of constitutive hepatic proteins. The goal of the hepatic acute-phase-response, which is mediated by cytokines and signal transcription factors, is to restore homeostasis. However, multiple studies have shown that a sustained or increased acute phase response is detrimental with the uncontrolled and prolonged action of acute phase proteins. The downregulation of constitutive hepatic proteins may further augment these detrimental effects. Research has focused on the attenuation of the inflammatory response using anti-inflammatory agents or antibodies against pro-inflammatory cytokines such as tumor necrosis (TNF), interleukin-1β (IL-1β), or their receptors. These approaches showed promising results in vitro and in animal models; however, when these approaches entered clinical trials it became evident that these promising animal data could not be substantiated in humans. A different approach is to attenuate the inflammatory cascade by the administration of growth factors. Growth factors exert anabolic effects and affect the inflammatory hepatic metabolism. The present review discusses the effect of recombinant human growth hormone, insulin-like growth factor-I, hepatocyte growth factor and insulin on the hepatic metabolism and homeostasis during inflammation and delineates the therapeutic benefit and limitation of growth factor administration in critically ill patients.

Original languageEnglish (US)
Pages (from-to)399-413
Number of pages15
JournalCurrent Drug Metabolism
Volume5
Issue number5
DOIs
StatePublished - Oct 2004

Fingerprint

Systemic Inflammatory Response Syndrome
Metabolism
Liver
Intercellular Signaling Peptides and Proteins
Acute-Phase Proteins
Animals
Pharmaceutical Preparations
Cytokines
Anabolic Agents
Acute-Phase Reaction
Hepatocyte Growth Factor
Human Growth Hormone
Immune system
Insulin-Like Growth Factor I
Interleukin-1
Muscle
Tumors
Proteins
Anti-Inflammatory Agents
Transcription Factors

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Effect of growth factors as therapeutic drugs on hepatic metabolism during the systemic inflammatory response syndrome. / Jeschke, Marc G.; Herndon, David.

In: Current Drug Metabolism, Vol. 5, No. 5, 10.2004, p. 399-413.

Research output: Contribution to journalArticle

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