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Leukoregulin, a novel cytokine enhances the anti-herpesvirus actions of acyclovir.

Abstract
Leukoregulin is a naturally occurring immunologic cytokine which increases membrane permeability and drug uptake in tumor cells but not in normal cells. In this paper we show that leukoregulin also increases membrane permeability of Herpes simplex virus type 1 (HSV-1)-infected cells. More importantly, we demonstrate that leukoregulin significantly enhances the ability of acyclovir (acycloguanosine, ACV) to inhibit the cellular release of infectious HSV-1. The ability of 1-100 microM ACV to inhibit infectious HSV-1 production is increased up to 100-fold when HSV-1-infected human amnion (WISH) cells are treated with 5 units leukoregulin/ml and ACV 3 hr after virus infection. Under these conditions, leukoregulin alone is unable to inhibit HSV-1 infectivity. In addition, three unrelated cytokines, interleukin-1 alpha (IL-1), interferon (IFN)-alpha and IFN-gamma lack the ability to enhance the anti-HSV actions of ACV when their treatment is initiated after HSV-1 infection. These findings demonstrate that a combination of immunotherapy and chemotherapy can produce a substantial inhibition of herpesvirus replication and provide a rationale for the application of this approach to the interventive treatment of virus infection.
AuthorsJ J Hooks, B Detrick, C H Evans
JournalClinical immunology and immunopathology (Clin Immunol Immunopathol) Vol. 60 Issue 2 Pg. 244-53 (Aug 1991) ISSN: 0090-1229 [Print] United States
PMID1649027 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Interferon Type I
  • Interleukin-1
  • Lymphokines
  • leukoregulin
  • Interferon-gamma
  • Acyclovir
Topics
  • Acyclovir (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Cell Membrane Permeability (drug effects)
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Flow Cytometry
  • Interferon Type I (pharmacology)
  • Interferon-gamma (pharmacology)
  • Interleukin-1 (pharmacology)
  • Lymphokines (pharmacology)
  • Simplexvirus (drug effects, pathogenicity, physiology)
  • Virus Replication (drug effects)

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