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 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.
Germinario
R J
RJ
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
DeSantis
T
T
Wainberg
M A
MA
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005312:Fetal Blood; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
D007328:Insulin; D007334:Insulin-Like Growth Factor I