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. 2006 Oct;44(4):896-906.
doi: 10.1002/hep.21312.

Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes

Sean E Doyle  1 , Heidi Schreckhise, Kien Khuu-Duong, Katherine Henderson, Robert Rosler, Harold Storey, Lena Yao, Hong Liu, Fariba Barahmand-pour, Pallavur Sivakumar, Chung Chan, Carl Birks, Don Foster, Christopher H Clegg, Perdita Wietzke-Braun, Sabine Mihm, Kevin M Klucher
Affiliations

Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes

Sean E Doyle et al. Hepatology. 2006 Oct.

Abstract

Interleukin-28A (IL-28A), IL-28B and IL-29 are a family of class II cytokines that stimulate antiviral responses through a heterodimeric receptor that is distinct from the type I interferon (IFN) receptor. To better understand how this newly described family of cytokines regulates the antiviral state, we compared various cellular responses elicited by IL-29 and IFN-alpha. Here we show that these cytokines stimulate similar patterns of signal transducer and activator of transcription 1 (STAT-1), -2, -3, and -5 phosphorylation and nearly identical patterns of gene expression when analyzed in two distinct cell types by microarray analysis. Interestingly, the IL-29 receptor is preferentially expressed on primary hepatocytes within normal liver and pegylated forms of IL-29 and IFN-alpha induced equivalent 2'5' oligoadenylate synthetase (OAS) and MX1 gene expression in this cell type. Pegylated IL-29 also produced a significant reduction in human hepatitis B and hepatitis C viral load in vitro and reduced the cytopathic effect caused by the fully replicating flavivirus, West Nile virus. In conclusion, IL-29 and IFN-alpha stimulate identical antiviral responses despite their utilization of different receptors. This fact, combined with significant receptor expression in hepatitis virus-infected livers, suggests that IL-29 may have therapeutic value against chronic viral hepatitis in human patients.

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