Interleukin-2 inhibits HIV-1 replication in human macrophages by modulating expression of CD4 and CC-chemokine receptor-5.
OBJECTIVE
To determine the effect of recombinant human interleukin (IL)-2 on HIV-1 replication and macrophage colony stimulating factor (M-CSF) production by HIV-1-infected monocyte-derived macrophages (MDM).


METHODS
Therapeutic use of IL-2 increases the number and function of CD4+ T cells. IL-2 also increases M-CSF production and M-CSF receptor expression by human monocytes, but the subsequent effects on HIV-1 replication in MDM have yet to be determined. MDM from HIV-1-seronegative donors were cultured in the presence and absence of IL-2 and infected with HIV-1. Harvested supernatants were monitored for reverse transcriptase activity and M-CSF production.


RESULTS
Reverse transcriptase activity was significantly lower when MDM cultures were treated with IL-2 for 10 days prior to infection with HIV-1. IL-2 did not stimulate production of inhibitory chemokines or cytokines, but FACS analysis revealed that expression of CD4, the primary HIV-1 receptor, and CC-chemokine receptor-5, a coreceptor used by macrophage-tropic viruses, are down modulated after treatment with IL-2.


CONCLUSIONS
IL-2 may not only be of benefit in restoring immune function in AIDS patients, but may also help to prevent the infection of healthy macrophages by decreasing their expression of HIV-1 receptors.
Kutza
J
J
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20852, USA.
Hayes
M P
MP
Clouse
K A
KA
D015704:CD4 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication
D015704:CD4 Antigens; D018925:Chemokines; D016207:Cytokines; D007376:Interleukin-2; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D054303:HIV Reverse Transcriptase