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. 1996 Oct;70(10):7103–7107. doi: 10.1128/jvi.70.10.7103-7107.1996

Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo.

D P Sharma 1, A J Ramsay 1, D J Maguire 1, M S Rolph 1, I A Ramshaw 1
PMCID: PMC190762  PMID: 8794356

Abstract

Interleukin-4 (IL-4) promotes the growth of Th2-type cells while down regulating the development of Th1-type cells. It has been suggested that the actions of this factor inhibit Th1-type effector activity in vivo and may underlie the development of diseases normally controlled by cell-mediated immune responses. Here, we show that clearance of recombinant vaccinia viruses (VV) engineered to express the gene for murine IL-4 is markedly delayed in mice compared with control recombinant VV. While antiviral antibody levels and NK activity in mice given control virus or IL-4-expressing virus were similar, antiviral cytotoxic T-lymphocyte responses were profoundly suppressed throughout the course of infection with the latter. Limiting dilution analysis of IL-4-virus-infected spleens revealed a marked reduction in numbers of cytotoxic T-lymphocyte precursors. Furthermore, reverse transcriptase PCR analysis of splenic mRNA prepared from mice infected with the IL-4-expressing VV showed a marked down regulation of IL-12, gamma interferon, and IL-2 gene expression compared with that from mice given control virus. IL-4 also inhibited the production of nitric oxide (NO), a potent mediator of antimicrobial activity. Together, these data show that IL-4 markedly suppresses the development of antiviral cell-mediated immune responses in vivo with deleterious effects on virus clearance.

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