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

John J. Hooks, Barbara Detrick, Charles H. Evans

Research output: Contribution to journalArticle

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 μM 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 α (IL-1), interferon (IFN)-α and IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)244-253
Number of pages10
JournalClinical Immunology and Immunopathology
Volume60
Issue number2
DOIs
StatePublished - 1991
Externally publishedYes

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Acyclovir
Herpesviridae
Human Herpesvirus 1
Cytokines
Virus Diseases
Interferons
Permeability
Amnion
Membranes
Combination Drug Therapy
Interleukin-1
Immunotherapy
leukoregulin
Therapeutics
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pathology and Forensic Medicine

Cite this

Leukoregulin, a novel cytokine enhances the anti-herpesvirus actions of acyclovir. / Hooks, John J.; Detrick, Barbara; Evans, Charles H.

In: Clinical Immunology and Immunopathology, Vol. 60, No. 2, 1991, p. 244-253.

Research output: Contribution to journalArticle

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