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

Abstract

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.