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

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.