Interferon beta modulates endothelial damage in patients with cardiac persistence of human parvovirus b19 infection

J Infect Dis. 2010 Mar 15;201(6):936-45. doi: 10.1086/650700.

Abstract

Background: In a phase 1 study, we investigated whether interferon beta reduced endothelial damage in patients with cardiac persistence of human parvovirus B19 (B19V) infection.

Methods and results: In vitro, B19V infected cultivated endothelial cells (ECs), which led to a reduction in their viability (P = .007). Interferon beta suppressed B19V replication by 63% (P = .008) in ECs and increased their viability (P = .021). Circulating mature apoptotic ECs (CMAECs [CD45(-)CD146(+) cells expressing von Willebrand factor and annexin V]) and circulating progenitor cells (CPCs [CD34(+)KDR(+) cells]) were quantified by flow cytometry in 9 symptomatic patients with cardiac B19V infection before and after 6 months of interferon beta therapy (16 MU) and were compared to levels in 9 healthy control subjects. Endothelial dysfunction was measured using flow-mediated dilatation of the forearm. Patients with B19V persistence had significantly higher (P = .04) levels of CMAECs than did control subjects, which normalized after treatment (mean +/- standard deviation, 0.06% +/-0.08% vs 0.01% +/- 0.006%; P = .008). Similar improvement was shown for flow-mediated dilatation (P = .04) in the treatment group only (P = .017 for the comparison with untreated patients with B19V persistence n = 5). There were significantly higher numbers of CPCs in patients with B19V persistence before therapy (mean +/- standard deviation, 0.04% +/- 0.05% vs 0.01% +/- 0.004%; P = .02; than in control subjects, which normalized after treatment (P = .03).

Conclusion: Thus, we present (for the first time, to our knowledge) a modulation of virally induced chronic endothelial damage-specifically, EC apoptosis and endothelial regeneration.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cardiovascular Diseases / prevention & control*
  • Cardiovascular Diseases / virology
  • Cell Line
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology
  • Endothelial Cells / virology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / virology
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-beta / pharmacology
  • Interferon-beta / therapeutic use*
  • Male
  • Middle Aged
  • Parvoviridae Infections / complications
  • Parvoviridae Infections / drug therapy*
  • Parvovirus B19, Human / drug effects*
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Interferon-beta