EFFICACY OF AN INSULIN-LIKE-GROWTH-FACTOR INTERLEUKIN-3 FUSION PROTEIN IN REVERSING THE HEMATOPOIETIC TOXICITY ASSOCIATED WITH AZIDOTHYMIDINE IN MICE

The effect of 406, a novel fusion protein between the N-terminal seque nce of the insect insulin-like peptide, bombyxin, human insulin-like g rowth factor II and mouse interleukin 3 was investigated in its capaci ty to abrogate the toxic effects of azidothymidine (AZT) in C57BL/6 mi ce. Mice receiving 2.5 mg/ml AZT in their drinking water were concurre ntly treated with daily s.c. injections of 14, 140 or 1400 ng 406 for 4 wk. AZT-treated mice had a lower total weight, hemoglobin content an d white blood cells than non treated controls. 406 significantly incre ased the number of circulating white blood cells at all doses, and the optimal effects were observed at a dose of 140 ng/mouse. Using this o ptimal dose, 406 completely abrogated the AZT-mediated weight loss, Th e effects on erythroid cells depended on the severity of the AZT-induc ed anemia, The amounts of hemoglobin were equal or slightly lower than those of controls under conditions of mild anemia, but were significa ntly higher than controls under conditions of severe anemia. 406 signi ficantly increased the number of all hematopoietic colony-forming cell s in bone marrow and spleen, but the effects were particularly strikin g in granulocyte-macrophage precursors. Blood glucose levels did not c hange at optimal or suboptimal 406 doses but increased at a dose of 1, 4 mu g/mouse. These experiments demonstrate the usefulness of these IG F-cytokine fusion proteins, whose low cost production represents a sig nificant advantage for future in vivo studies.