IL-4 and IL-13 have overlapping but distinct effects on HIV production in monocytes.
In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48-72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the U1 and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimately stimulated cytolysis of HIV-infected monocytes as well as increased apoptosis of U1. In the presence of tumor necrosis factor alpha or IL-6, which upregulate HIV expression, IL-13 could no longer suppress HIV expression. These results indicate that IL-4 and IL-13, although closely related in modulating monocyte function, can have divergent effects on HIV expression in monocytes. Collectively, these data suggest that there exists a complex cytokine tissue environment with positive regulators of HIV expression able to override negative regulators.
Mikovits
J A
JA
Biological Carcinogenesis and Development Program, Program Resources/DynCorp, Inc., Labege, France.
Meyers
A M
AM
Ortaldo
J R
JR
Minty
A
A
Caput
D
D
Ferrara
P
P
Ruscetti
F W
FW
D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006678:HIV / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D018793:Interleukin-13; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D009000:Monocytes / Q000737:chemistry / Q000166:cytology* / Q000382:microbiology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004279:DNA, Viral; D018793:Interleukin-13; D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4