Human leukemia inhibitory factor inhibits development of experimental atherosclerosis.

Abstract

The effect of human leukemia inhibitory factor (hLIF) on the development of atherosclerosis was investigated in an experimental animal model. Two conditions were examined: one in which lesions could arise because of the influence of both "injury" (cuffed vessel) and diet and one in which only the effect of diet could be significant in other areas of the vasculature (aorta). At time zero, the right carotid artery of rabbits (n = 32) was ensheathed in a soft Silastic cuff, and an osmotic minipump (2-mL capacity; 2.5 microL/h; 28 days) containing either hLIF or saline was inserted into the peritoneal cavity. Rabbits were divided into four groups (n = 8): group 1 received normal diet/saline; group 2, normal diet/LIF (30 micrograms.kg-1.d-1); group 3, 1% cholesterol diet/saline; and group 4, 1% cholesterol diet/LIF (30 micrograms.kg-1.d-1). After 28 days, the cholesterol diet (group 3) resulted in a sixfold increase in plasma cholesterol level compared with group 1 rabbits on a normal diet (3.80 +/- 0.50 versus 0.55 +/- 0.01 mmol/L). This was significantly lower (P = .01) with hLIF treatment in group 4 rabbits (2.80 +/- 0.44 mmol/L). Group 2 rabbits had higher aortic tissue cholesterol levels (1.40 +/- 0.35 mg/g) compared with group 1 rabbits on a normal diet (0.10 +/- 0.06 mg/g) (P = .01), whereas hLIF treatment decreased tissue cholesterol levels by 60% in group 4 rabbits (0.60 +/- 0.05 mg/g) (P = .01). Group 3 rabbits developed lipid-filled lesions covering 63.25 +/- 17.66% of the thoracic aorta surface, whereas lesions were significantly reduced (9.88 +/- 8.79%) (P = .01) with LIF treatment (group 4).(ABSTRACT TRUNCATED AT 250 WORDS)