The differential activity of interferon-α subtypes is consistent among distinct target genes and cell types

Cytokine. 2011 Jan;53(1):52-9. doi: 10.1016/j.cyto.2010.09.006. Epub 2010 Oct 12.


IFN-α proteins have been described to originate from 14 individual genes and allelic variants. However, the exceptional diversity of IFN-α and its functional impact are still poorly understood. To characterize the biological activity of IFN-α subtypes in relation to the cellular background, we investigated the effect of IFN-α treatment in primary fibroblasts and endothelial cells of vascular or lymphatic origin. The cellular response was evaluated for 13 distinct IFN-α proteins with respect to transcript regulation of the IFN-stimulated genes (ISGs) IFIT1, ISG15, CXCL10, CXCL11 and CCL8. The IFN-α proteins displayed a remarkably consistent potency in gene induction irrespective of target gene and cellular background which led to the classification of IFN-α subtypes with low (IFN-α1), intermediate (IFN-α2a, -4a, -4b, -5, -16, -21) and high (IFN-α2b, -6, -7, -8, -10, -14) activity. The differential potency of IFN-α classes was confirmed at the ISG protein level and the functional protection of cells against influenza virus infection. Differences in IFN activity were only observed at subsaturating levels of IFN-α proteins and did not affect the time course of ISG regulation. Cell-type specific responses were apparent for distinct target genes independent of IFN-α subtype and were based on different levels of basal versus inducible gene expression. While fibroblasts presented with a high constitutive level of IFIT1, the expression in endothelial cells was strongly induced by IFN-α. In contrast, CXCL10 and CXCL11 transcript levels were generally higher in endothelial cells despite a pronounced induction by IFN-α in fibroblasts. In summary, the divergent potency of IFN-α proteins and the cell-type specific regulation of individual IFN target genes may allow for the fine tuning of cellular responses to pathogen defense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interferon-alpha / classification*
  • Interferon-alpha / pharmacology*
  • Kinetics
  • Male
  • Organ Specificity / drug effects
  • Organ Specificity / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Antiviral Agents
  • Interferon-alpha
  • RNA, Messenger
  • Transcription Factors