16α-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: Initial enhancement leading to long-term suppression

Niels C Pedersen, Thomas W. North, Richard Rigg, Chris Reading, Joanne Higgins, Christian Leutenegger, Gary L. Henderson

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

16α-Bromo-epiandrosterone (epiBr), a synthetic derivative of the natural hormone dehyroepiandrosterone (DHEA), was evaluated for its effects on feline immunodeficiency virus (FIV) infection in experimental cats. The rationale for this study was based on the ability of DHEA to significantly reduce the mortality to viral infections in mice. DHEA and epiBr also have demonstrable in vitro anti-viral activity for both HIV-1 and FIV. Preliminary pharmacokinetic studies in cats demonstrated that subcutaneously injected epiBr was rapidly absorbed, completely metabolized, and nontoxic. Metabolites were excreted in both urine and feces, with the latter having the most complex pattern of breakdown products. Cats were then divided into four groups; two groups were infected with FIV and two uninfected. Two groups, one infected and one uninfected were treated on 5 consecutive days of weeks 0, 4, 8, 12 and 16 with epiBr. The remaining two groups were mock treated with the drug vehicle alone. Treatment started 1 week prior to infection and extended for 4 weeks after infection. Cats were observed for 20 weeks post-FIV infection. Infected cats had identical decreases in blood neutrophil and lymphocyte counts following, regardless of whether they were treated with epiBr or vehicle alone. The CD4/CD8 T-cell ratio was decreased following FIV exposure, but was significantly more decreased for the epiBr treated animals from week 2 post-infection onward. CD4+ T cells were decreased in FIV-infected cats treated with epiBr compared to their untreated cohort, while CD8+ T cells tended to be higher in treated animals. FIV infected cats that were treated with epiBr had over one-log higher virus loads at week 2 post-infection than non-epiBr treated cohorts. In spite of this enhanced initial viremia, the subsequent levels of virus in the blood were significantly lower in epiBr treated versus untreated animals. EpiBr treated cats had significantly higher FIV-p24 antibody responses than control cats receiving vehicle alone, although primary and secondary antibody responses to a T-cell dependent non-FIV antigen, keyhole limpet hemocyanin (KLH), were unaffected. EpiBr treatment significantly decreased the expected FIV-induced suppression of IL-12 p40 mRNA levels in peripheral blood mononuclear cells (PBMCs) observed at weeks 4, 5, 8, 9 and 16 post-infection, but had no influence on FIV-induced changes in IL-4, IL-6, IL-10, IFN-γ, MIP-1α and RANTES.

Original languageEnglish (US)
Pages (from-to)133-148
Number of pages16
JournalVeterinary Immunology and Immunopathology
Volume94
Issue number3-4
DOIs
StatePublished - Aug 15 2003

Fingerprint

Androsterone
Feline Immunodeficiency Virus
Investigational Therapies
Feline immunodeficiency virus
Viremia
viremia
Cats
cats
therapeutics
infection
Virus Diseases
T-lymphocytes
T-Lymphocytes
Infection
Viruses
Antibody Formation
Chemokine CCL5
viruses
animals
antibodies

Keywords

  • 16α-Bromo-epiandrosterone
  • Feline immunodeficiency virus
  • Immunomodulation

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Immunology
  • veterinary(all)

Cite this

16α-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia : Initial enhancement leading to long-term suppression. / Pedersen, Niels C; North, Thomas W.; Rigg, Richard; Reading, Chris; Higgins, Joanne; Leutenegger, Christian; Henderson, Gary L.

In: Veterinary Immunology and Immunopathology, Vol. 94, No. 3-4, 15.08.2003, p. 133-148.

Research output: Contribution to journalArticle

Pedersen, Niels C ; North, Thomas W. ; Rigg, Richard ; Reading, Chris ; Higgins, Joanne ; Leutenegger, Christian ; Henderson, Gary L. / 16α-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia : Initial enhancement leading to long-term suppression. In: Veterinary Immunology and Immunopathology. 2003 ; Vol. 94, No. 3-4. pp. 133-148.
@article{0eefd6e7d5eb4901beee53da1253aa0c,
title = "16α-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: Initial enhancement leading to long-term suppression",
abstract = "16α-Bromo-epiandrosterone (epiBr), a synthetic derivative of the natural hormone dehyroepiandrosterone (DHEA), was evaluated for its effects on feline immunodeficiency virus (FIV) infection in experimental cats. The rationale for this study was based on the ability of DHEA to significantly reduce the mortality to viral infections in mice. DHEA and epiBr also have demonstrable in vitro anti-viral activity for both HIV-1 and FIV. Preliminary pharmacokinetic studies in cats demonstrated that subcutaneously injected epiBr was rapidly absorbed, completely metabolized, and nontoxic. Metabolites were excreted in both urine and feces, with the latter having the most complex pattern of breakdown products. Cats were then divided into four groups; two groups were infected with FIV and two uninfected. Two groups, one infected and one uninfected were treated on 5 consecutive days of weeks 0, 4, 8, 12 and 16 with epiBr. The remaining two groups were mock treated with the drug vehicle alone. Treatment started 1 week prior to infection and extended for 4 weeks after infection. Cats were observed for 20 weeks post-FIV infection. Infected cats had identical decreases in blood neutrophil and lymphocyte counts following, regardless of whether they were treated with epiBr or vehicle alone. The CD4/CD8 T-cell ratio was decreased following FIV exposure, but was significantly more decreased for the epiBr treated animals from week 2 post-infection onward. CD4+ T cells were decreased in FIV-infected cats treated with epiBr compared to their untreated cohort, while CD8+ T cells tended to be higher in treated animals. FIV infected cats that were treated with epiBr had over one-log higher virus loads at week 2 post-infection than non-epiBr treated cohorts. In spite of this enhanced initial viremia, the subsequent levels of virus in the blood were significantly lower in epiBr treated versus untreated animals. EpiBr treated cats had significantly higher FIV-p24 antibody responses than control cats receiving vehicle alone, although primary and secondary antibody responses to a T-cell dependent non-FIV antigen, keyhole limpet hemocyanin (KLH), were unaffected. EpiBr treatment significantly decreased the expected FIV-induced suppression of IL-12 p40 mRNA levels in peripheral blood mononuclear cells (PBMCs) observed at weeks 4, 5, 8, 9 and 16 post-infection, but had no influence on FIV-induced changes in IL-4, IL-6, IL-10, IFN-γ, MIP-1α and RANTES.",
keywords = "16α-Bromo-epiandrosterone, Feline immunodeficiency virus, Immunomodulation",
author = "Pedersen, {Niels C} and North, {Thomas W.} and Richard Rigg and Chris Reading and Joanne Higgins and Christian Leutenegger and Henderson, {Gary L.}",
year = "2003",
month = "8",
day = "15",
doi = "10.1016/S0165-2427(03)00081-3",
language = "English (US)",
volume = "94",
pages = "133--148",
journal = "Veterinary Immunology and Immunopathology",
issn = "0165-2427",
publisher = "Elsevier",
number = "3-4",

}

TY - JOUR

T1 - 16α-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia

T2 - Initial enhancement leading to long-term suppression

AU - Pedersen, Niels C

AU - North, Thomas W.

AU - Rigg, Richard

AU - Reading, Chris

AU - Higgins, Joanne

AU - Leutenegger, Christian

AU - Henderson, Gary L.

PY - 2003/8/15

Y1 - 2003/8/15

N2 - 16α-Bromo-epiandrosterone (epiBr), a synthetic derivative of the natural hormone dehyroepiandrosterone (DHEA), was evaluated for its effects on feline immunodeficiency virus (FIV) infection in experimental cats. The rationale for this study was based on the ability of DHEA to significantly reduce the mortality to viral infections in mice. DHEA and epiBr also have demonstrable in vitro anti-viral activity for both HIV-1 and FIV. Preliminary pharmacokinetic studies in cats demonstrated that subcutaneously injected epiBr was rapidly absorbed, completely metabolized, and nontoxic. Metabolites were excreted in both urine and feces, with the latter having the most complex pattern of breakdown products. Cats were then divided into four groups; two groups were infected with FIV and two uninfected. Two groups, one infected and one uninfected were treated on 5 consecutive days of weeks 0, 4, 8, 12 and 16 with epiBr. The remaining two groups were mock treated with the drug vehicle alone. Treatment started 1 week prior to infection and extended for 4 weeks after infection. Cats were observed for 20 weeks post-FIV infection. Infected cats had identical decreases in blood neutrophil and lymphocyte counts following, regardless of whether they were treated with epiBr or vehicle alone. The CD4/CD8 T-cell ratio was decreased following FIV exposure, but was significantly more decreased for the epiBr treated animals from week 2 post-infection onward. CD4+ T cells were decreased in FIV-infected cats treated with epiBr compared to their untreated cohort, while CD8+ T cells tended to be higher in treated animals. FIV infected cats that were treated with epiBr had over one-log higher virus loads at week 2 post-infection than non-epiBr treated cohorts. In spite of this enhanced initial viremia, the subsequent levels of virus in the blood were significantly lower in epiBr treated versus untreated animals. EpiBr treated cats had significantly higher FIV-p24 antibody responses than control cats receiving vehicle alone, although primary and secondary antibody responses to a T-cell dependent non-FIV antigen, keyhole limpet hemocyanin (KLH), were unaffected. EpiBr treatment significantly decreased the expected FIV-induced suppression of IL-12 p40 mRNA levels in peripheral blood mononuclear cells (PBMCs) observed at weeks 4, 5, 8, 9 and 16 post-infection, but had no influence on FIV-induced changes in IL-4, IL-6, IL-10, IFN-γ, MIP-1α and RANTES.

AB - 16α-Bromo-epiandrosterone (epiBr), a synthetic derivative of the natural hormone dehyroepiandrosterone (DHEA), was evaluated for its effects on feline immunodeficiency virus (FIV) infection in experimental cats. The rationale for this study was based on the ability of DHEA to significantly reduce the mortality to viral infections in mice. DHEA and epiBr also have demonstrable in vitro anti-viral activity for both HIV-1 and FIV. Preliminary pharmacokinetic studies in cats demonstrated that subcutaneously injected epiBr was rapidly absorbed, completely metabolized, and nontoxic. Metabolites were excreted in both urine and feces, with the latter having the most complex pattern of breakdown products. Cats were then divided into four groups; two groups were infected with FIV and two uninfected. Two groups, one infected and one uninfected were treated on 5 consecutive days of weeks 0, 4, 8, 12 and 16 with epiBr. The remaining two groups were mock treated with the drug vehicle alone. Treatment started 1 week prior to infection and extended for 4 weeks after infection. Cats were observed for 20 weeks post-FIV infection. Infected cats had identical decreases in blood neutrophil and lymphocyte counts following, regardless of whether they were treated with epiBr or vehicle alone. The CD4/CD8 T-cell ratio was decreased following FIV exposure, but was significantly more decreased for the epiBr treated animals from week 2 post-infection onward. CD4+ T cells were decreased in FIV-infected cats treated with epiBr compared to their untreated cohort, while CD8+ T cells tended to be higher in treated animals. FIV infected cats that were treated with epiBr had over one-log higher virus loads at week 2 post-infection than non-epiBr treated cohorts. In spite of this enhanced initial viremia, the subsequent levels of virus in the blood were significantly lower in epiBr treated versus untreated animals. EpiBr treated cats had significantly higher FIV-p24 antibody responses than control cats receiving vehicle alone, although primary and secondary antibody responses to a T-cell dependent non-FIV antigen, keyhole limpet hemocyanin (KLH), were unaffected. EpiBr treatment significantly decreased the expected FIV-induced suppression of IL-12 p40 mRNA levels in peripheral blood mononuclear cells (PBMCs) observed at weeks 4, 5, 8, 9 and 16 post-infection, but had no influence on FIV-induced changes in IL-4, IL-6, IL-10, IFN-γ, MIP-1α and RANTES.

KW - 16α-Bromo-epiandrosterone

KW - Feline immunodeficiency virus

KW - Immunomodulation

UR - http://www.scopus.com/inward/record.url?scp=0142061180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142061180&partnerID=8YFLogxK

U2 - 10.1016/S0165-2427(03)00081-3

DO - 10.1016/S0165-2427(03)00081-3

M3 - Article

C2 - 12909410

AN - SCOPUS:0142061180

VL - 94

SP - 133

EP - 148

JO - Veterinary Immunology and Immunopathology

JF - Veterinary Immunology and Immunopathology

SN - 0165-2427

IS - 3-4

ER -