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.


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).


CONCLUSIONS
Thus, we present (for the first time, to our knowledge) a modulation of virally induced chronic endothelial damage-specifically, EC apoptosis and endothelial regeneration.
Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany. caroline.schmidt-lucke@charite.de
Caroline
C
Schmidt-Lucke
Frank
F
Spillmann
Thomas
T
Bock
Uwe
U
Kühl
Sophie
S
Van Linthout
Heinz-Peter
HP
Schultheiss
Carsten
C
Tschöpe
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control* / Q000821:virology; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000821:virology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000150:complications / Q000188:drug therapy*; D016732:Parvovirus B19, Human / Q000187:drug effects*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
D000998:Antiviral Agents; D016899:Interferon-beta