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

• Published in: Journal of leukocyte biology Vol. 56; no. 3; p. 340
• Main Authors: Mikovits, J A, Meyers, A M, Ortaldo, J R, Minty, A, Caput, D, Ferrara, P, Ruscetti, F W
• Format: Journal Article
• Language: English
• Published: United States 01-09-1994
• Subjects: Cells, Cultured; DNA, Viral - analysis; DNA, Viral - genetics; Gene Expression Regulation, Viral - drug effects; HIV - genetics; HIV - isolation & purification; Humans; Interleukin-13; Interleukin-4 - pharmacology; Interleukin-6 - pharmacology; Interleukins - pharmacology; 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
• 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 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.