Insulin-Like Growth Factor 1 and Insulin Inhibit HIV Type 1 Replication in Cultured Cells

Abstract

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 × 10^-10 M) while that of insulin was observed at supraphysiological concentrations (8 × 10^-7 M). The EC₅₀ for IGF-1 was found to be in the physiological range (2.5-4.5 × 10^-9 M) while that for insulin was considerably higher (1.1-3.3 × 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 × 10^-10 to 1.6 × 10^-8 M demonstrated no inhibition of HIV-1 replication, while IGF-1 inhibited p24 antigen production 49 and 42% at 1.3 × 10^-9 and 1.3 × 10^-8 M IGF-1, respectively. These results suggest that IGF-1 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.