Leukemia inhibitory factor is a mediator of Escherichia coli lipopolysaccharide-induced acute thymic atrophy.

Journal Article (Journal Article)

Septic shock in animals and humans is associated with thymic atrophy and generalized lymphocyte apoptosis that impairs T cell responses. Injection of animals with E. coli lipopolysaccharide (LPS) mimics bacterial sepsis-induced thymic atrophy. Leukemia inhibitory factor (LIF) induces pituitary ACTH release in vivo, and LIF administration to mice induces acute thymic atrophy. We have investigated the role of LIF in LPS-induced thymic atrophy. LPS significantly elevated serum LIF within 1 h and induced thymic LIF mRNA within 6 h. Moreover, pretreatment of mice with anti-LIF antibody significantly reduced LPS-induced thymic atrophy. Using adrenalectomized mice and 17-day fetal thymic organ cultures treated with the steroidogenic enzyme inhibitor metyrapone, we demonstrated that LIF induced both systemic and intrathymic corticosteroid production. These data demonstrate systemic and intrathymic pathways of E. coli LPS-induced acute thymic atrophy mediated by LIF and corticosteroids.

Full Text

Duke Authors

Cited Authors

  • Sempowski, GD; Rhein, ME; Scearce, RM; Haynes, BF

Published Date

  • November 2002

Published In

Volume / Issue

  • 32 / 11

Start / End Page

  • 3066 - 3070

PubMed ID

  • 12385026

Pubmed Central ID

  • 12385026

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/1521-4141(200211)32:11<3066::AID-IMMU3066>3.0.CO;2-J


  • eng

Conference Location

  • Germany