MEASUREMENT OF LEUKEMIA INHIBITORY FACTOR IN BIOLOGICAL-FLUIDS BY RADIOIMMUNOASSAY

Leukemia inhibitory factor (LIF) exhibits multiple biological activiti es in various tissues, and we have shown that LIF activates POMC gene transcription in response to immune signals. As higher serum levels of LIF have been reported in septicemia, we measured LIF values in biolo gical fluids by RIA. Immunoreactive LIF was detected in 303 of 428 hum an serum samples. Circulating LIF detection rates were 69% in acute in flammatory diseases, 83% in chronic inflammatory diseases, 61% in noni nflammatory diseases, and 90% in cancer patients. Serum concentrations of human LIF was higher in patients with inflammatory disease than in noninflammatory disease (0.80 +/- 0.10 vs. 0.53 +/- 0.02 ng/mL; P < 0 .05) or in cancer patients (0.44 +/- 0.06; P < 0.05). Higher serum hum an LIF levels were found in septicemia (0.78 +/- 0.14 ng/mL), pneumoni a (0.80 +/- 0.10 ng/mL), acute bronchitis (0.88 +/- 0.09 ng/mL), other infections (1.01 +/- 0.17 ng/mL), and systemic lupus erythematosus (S LE; 0.79 +/- 0.06 ng/mL). In 7 septicemia patients, Gram-negative infe ction was associated with higher LIF levels (1.06 +/- 0.16 ng/mL) than was Gram-positive infection (0.58 +/- 0.14 ng/mL). In patients with a cute inflammatory disease, serum LIF levels decreased within several d ays after hospitalization. To test circulating mouse (m) LIF changes i n response to inflammatory stress, lipopolysaccharide (LPS) was inject ed ip to mice. LPS increased serum mLIF values concordantly with ACTH levels. After ip injection of 80 mu g LPS, serum mLIF increased by 144 % (P < 0.05), 173% (P < 0.05), and 134% at 30, 90, and 120 min respect ively. In vitro, however, LPS did not increase ACTH and mLIF secretion from dispersed mouse primary pituitary cells. These results suggest t hat LIF is an important participant in the pathogenesis of the acute i nflammatory response. The elevated serum LIF levers observed in inflam mation do not appear to originate from the pituitary.