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Endogenous leukemia inhibitory factor attenuates endotoxin response.

Marietta A Weber1, Silvia Schnyder-Candrian, Bruno Schnyder

  • 1Cancer and Developmental Biology Laboratory, NCI-FCRDC, Frederick, MD, USA.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|February 11, 2005
PubMed
Summary

Endogenous leukemia inhibitory factor (LIF) protects against endotoxic shock. LIF deficiency increases sensitivity to lipopolysaccharide (LPS), leading to severe organ damage and mortality.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Pathophysiology

Background:

  • Leukemia inhibitory factor (LIF) is implicated in inflammatory responses.
  • Its precise role in host defense during systemic inflammation remains unclear.

Purpose of the Study:

  • To investigate the endogenous role of LIF in endotoxic shock.
  • To determine LIF's protective function in host defense mechanisms.

Main Methods:

  • Utilized leukemia inhibitory factor-deficient (LIF-/-) mice and wild-type (LIF+/+) littermates.
  • Employed a lipopolysaccharide (LPS)/D-galactosamine (D-Gal) sensitization model for endotoxemia.
  • Assessed sensitivity to LPS, organ damage (hepatic necrosis), blood cell counts, and survival rates.
  • Quantified serum levels of pro-inflammatory cytokines (TNF-alpha, IL-6) and anti-inflammatory cytokine (IL-10).

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Main Results:

  • LIF-/- mice exhibited significantly heightened sensitivity to LPS, evidenced by increased hepatic necrosis, thrombocytopenia, and leukopenia.
  • Mortality was accelerated in LIF-/- mice compared to wild-type controls.
  • LPS challenge led to a 10-fold increase in serum TNF-alpha and IL-6 levels, coupled with reduced IL-10 production in LIF-/- mice.

Conclusions:

  • Endogenous LIF plays a crucial protective role in attenuating the endotoxic shock response.
  • LIF enhances basal acute phase protein expression and IL-10 production, which downregulates TNF-alpha synthesis.
  • LIF confers partial protection against endotoxemia, highlighting its importance in host defense.