The Inhibition of HIV Replication in Monocytes by Interleukin 10 Is Linked to Inhibition of Cell Differentiation

The effect of exogenous recombinant interleukin 10 on the replication of low-passage HIV-1 strains in blood-derived monocytes and monocyte-derived-macrophages (MDMs) was examined at various stages of cell maturation after adherence to the plastic substrate. Interleukin 10 inhibited extracellular production of HIV-1 to a greater degree in monocytes infected within 24 hr of adherence than those infected at 5–7 days. Inhibition of viral production as extracellular p24 antigen was most marked when interleukin 10 was preincubated with monocytes for 24–96 hr (optimum, 48 hr), and increased between 2 and 100 ng/ml. Neutralizing antibody to IL-10 reversed the inhibition. Inhibition of HIV production from monocytes and macrophages was maximal at 1 week after a single addition of cytokine, but then HIV production rose to control levels. Interleukin 10 was also found to inhibit reversibly the normal increase in size and maturation of both uninfected and HIV-infected monocytes during 10–15 days of adherence. In addition, cytoplasmic and membrane expression of CD26, a marker of macrophage maturation, was markedly inhibited but the proportion of detaching, apoptotic, or necrotic cells was also not increased. Hence, interleukin 10 reversibly inhibits both monocyte maturation and HIV production from infected monocytes with similar kinetics, suggesting that inhibition of monocyte maturation by IL-10 may have a marked effect of HIV production by these cells.