[Do antisense oligonucleotides improve viral immunopathology?].
BACKGROUND
Tumor necrosis factor (TNF)-alpha as a proinflammatory cytokine is of great importance during the development of herpes simplex virus-1 keratitis (HSK). In this study the local administration of antisense oligonucleotides (ASON) targeting TNF-alpha was examined for its usefulness in ameliorating this disease.


METHODS
Uptake and efficacy of the oligonucleotides were studied in vitro by fluorescence microscopy and flow cytometry. Substance- and sequence-specific influences on the development of HSK were scrutinized in an animal model.


RESULTS
Quick and stable uptake of FITC-labeled ASON by isolated spleen and lymph node cells was proved. The production of TNF-alpha by these cells after stimulation with HSV antigen or concanavalin A (ConA) was clearly downregulated after addition of ASON. In vivo, incidence and development of HSK were ameliorated after subepithelial corneal injection of ASON targeting TNF-alpha. When buffer and control oligonucleotides were given, no significant influence on the disease was found.


CONCLUSIONS
The ASON effectively reduced TNF-alpha secretion in vitro and suppressed the development of experimental HSK in vivo.
Wasmuth
S
S
Ophtha-Lab und Augenabteilung, St. Franziskus Hospital, Münster.
Bauer
D
D
Steuhl
K P
KP
Heiligenhaus
A
A
D000818:Animals; D001682:Biological Availability; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002522:Chlorocebus aethiops; D003315:Cornea / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000472:pathogenicity*; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology; D014709:Vero Cells; D014776:Virus Cultivation
D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha