LEUKEMIA INHIBITORY FACTOR PRODUCES HYPERCALCEMIA IN RATS WITHOUT ALTERING BONE HISTOMORPHOMETRY OF THE TIBIA

Leukemia inhibitory factor (LIF) is a single-chain polypeptide that pr eviously was shown in mice to produce hypercalcemia and influence skel etal growth and turnover. We performed dose-response studies to determ ine if LIF alters the serum calcium or histomorphometry of the tibia i n growing male rats. Forty animals were divided into five groups of ei ght animals each. Recombinant human LIF, 0.01, 0.1, 1, or 10 mu g/100 g body wt, or vehicle was administered daily S.C. for 3 weeks. Compare d with controls it was found that LIF increased mean serum calcium at the two highest doses (11.4 +/- 0.1 versus 10.8 +/- 0.1 mg/dl, P = 0.0 005 by one-way analysis of variance (ANOVA) but did not alter static o r dynamic measurements of histomorphometry or length of the tibia. We conclude that in growing rats, high systemic concentrations of LIF res ult in hypercalcemia with no changes in bone turnover.