Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor.

Abstract

Cells of the murine hemopoietic cell line FDC-P1 were multiply infected with a retroviral construct containing cDNA encoding the leukemia inhibitory factor (LIF) to produce cells secreting high levels of LIF. Injection of these cells to unirradiated or irradiated syngeneic DBA/2 mice resulted in animals engrafted with LIF-producing cells in the marrow, spleen, and lymph nodes and with elevated serum LIF levels. These mice developed within 12-70 days a fatal syndrome characterized by cachexia, excess new bone formation, calcification in heart and skeletal muscle, pancreatitis, thymus atrophy, and abnormalities in the adrenal cortex and ovarian corpora lutea. Injection of mice with control FDC-P1 cells led to comparable organ engraftment, but the mice developed none of these lesions. The observations suggest that LIF may be a potent cachexia-inducing agent and may have marked effects on osteoblasts and calcium metabolism.