Synergistic anti-HSV effect of tumor necrosis factor alpha and interferon gamma in human corneal fibroblasts is associated with interferon beta induction

Shun Hua Chen, John E. Oakes, Robert N. Lausch

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

HSV-1 (17) replicated to high titer in human corneal fibroblasts (> 108 PFU/105 cells) following infection at one PFU per 100 cells. Pretreatment of the cells for 24 h with 50 U/ml recombinant human tumor necrosis factor alpha (TNF-α) or 5 IU/ml of human interferon gamma (IFN-γ) resulted in only modest reduction (2- to 19-fold) in virus yield. However, when the two cytokines were combined the antiviral effect was dramatically increased. There was > 1000-fold reduction in virus titer in 8 of 8 trials. In contrast, the combinations of 50 U/ml TNF-α with 5 IU/ml IFN-α or IFN-β did not produce a synergistic effect. The pronounced synergistic antiviral activity of TNF-α + IFN-γ could be demonstrated in fibroblast cultures from different donors, and HSV-2 as well as HSV-1 strains were inhibited. There was no evidence that dual cytokine treatment was toxic for uninfected or HSV-infected cells. Insight into the mechanism responsible for the synergistic effect was provided by the observation that TNF-α + IFN-γ induced IFN-β. In addition, anti-IFN-β but not anti-IFN-α antibodies could reverse the antiviral effect, and reconstitution with IFN-β could duplicate the phenomenon. We conclude that the combination of TNF-α and IFN-γ at low concentrations can exert a powerful anti-herpes effect in human corneal fibroblasts which can be chiefly attributed to the induction of IFN-β.

Original languageEnglish
Pages (from-to)15-29
Number of pages15
JournalAntiviral Research
Volume22
Issue number1
DOIs
Publication statusPublished - 1993 Sep

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

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