IL-4 and IL-13 have overlapping but distinct effects on HIV production in monocytes

• Published in: Journal of leukocyte biology 1994-09, Vol.56 (3), p.340-346
• Main Authors: Mikovits, Judy A., Meyers, Anne M., Ortaldo, John R., Minty, Adrian, Caput, Daniel, Ferrara, Pascual, Ruscetti, Francis W.
• Format: Article
• Language: English
• Subjects: Cells, Cultured; cytokines; DNA, Viral - analysis; DNA, Viral - genetics; Gene Expression Regulation, Viral - drug effects; HIV - genetics; HIV - isolation & purification; HIV regulation; human immunodeficiency virus 1; Humans; Interleukin-13; Interleukin-4 - pharmacology; Interleukin-6 - pharmacology; Interleukins - pharmacology; monocytes; Monocytes - chemistry; Monocytes - cytology; Monocytes - microbiology; RNA, Messenger - analysis; RNA, Messenger - genetics; RNA, Viral - analysis; RNA, Viral - genetics; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.56.3.340

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 α 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. J. Leukoc. Biol. 56: 340–346; 1994.