Germinario R J, DeSantis T, Wainberg M A
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
AIDS Res Hum Retroviruses. 1995 May;11(5):555-61. doi: 10.1089/aid.1995.11.555.
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 EC50 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-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.
胰岛素样生长因子1和胰岛素主要被视为代谢和生长调节激素，研究发现它们可抑制HIV-1在培养的脐血单核细胞和慢性HIV感染的U937细胞中的复制。胰岛素样生长因子1在生理浓度或更低浓度（1.7×10⁻¹⁰ M）时即可发挥作用，而胰岛素则需在超生理浓度（8×10⁻⁷ M）时才会产生作用。胰岛素样生长因子1的半数有效浓度（EC50）处于生理范围（2.5 - 4.5×10⁻⁹ M），而胰岛素的EC50则高得多（1.1 - 3.3×10⁻⁶ M）。本研究中所使用浓度的胰岛素样生长因子1和胰岛素对细胞均无毒性。此外，胰岛素样生长因子1和胰岛素在体外对纯化的逆转录酶均无抑制活性。浓度从1.6×10⁻¹⁰到1.6×10⁻⁸ M的表皮生长因子未显示出对HIV-1复制的抑制作用，而胰岛素样生长因子1在1.3×10⁻⁹ M和1.3×10⁻⁸ M时分别抑制p24抗原产生49%和42%。这些结果表明，胰岛素样生长因子1在某些条件下于生理浓度时对HIV-1复制具有显著抑制作用。这可能对HIV-1感染患者具有治疗价值。
