INSULIN-LIKE GROWTH-FACTOR-1 AND INSULIN INHIBIT HIV TYPE-1 REPLICATION IN CULTURED-CELLS

Insulin-like growth factor 1 and insulin, considered primarily as metabolic and growth modulatory hormones, were found to inhibit the replication of HIV-1 in cultured cord blood mononuclear cells and chronically HIV-infected U937 cells, The effect of IGF-1 was seen at physiological concentrations or lower (1.7 x 10(-10) M) while that of insulin was observed at supraphysiological concentrations (8 x 10(-7) M), The EC(50) for IGF-1 was found to be in the physiological range (2.5-4.5 x 10(-9) M) while that for insulin was considerably higher (1.1-3.3 x 10(-6) M), Insulin-like growth factor 1 and insulin at the concentrations employed exhibited no toxicity on the cells used in these studies, Furthermore, neither IGF-1 nor insulin exhibited any inhibitory activity on purified reverse transcriptase in vitro. Epidermal growth factor from 1.6 x 10-(10) to 1.6 x 10(-8) M demonstrated no inhibition of HIV-1 replication, while IGF-1 inhibited p24 antigen production 49 and 42% at 1.3 x 10(-9) and 1.3 x 10(-8) M IGF-1, respectively, These results suggest that IGF-I under certain conditions has significant inhibitory effects on HIV-1 replication at physiological concentrations, This may prove to be of therapeutic value in patients infected with HIV-1.