PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity

Marla J. Keller, Esmeralda Guzman, Ehsan Hazrati, Andrea Kasowitz, Natalia V. Cheshenko, Sylvan Wallenstein, Amy L. Cole, Alexander M. Cole, Albert T. Profy, Charles R. Wira, Kathleen Hogarty, Betsy Herold

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

OBJECTIVE: Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective of this study was to examine the effect of 14 daily applications of 0.5% PRO 2000 or placebo gel on mediators of mucosal immunity and intrinsic antimicrobial activity. DESIGN AND METHODS: A randomized, prospective, double-blind, placebo-controlled study was conducted among 24 healthy, abstinent women. Levels of cytokines, chemokines, defensins, and other protective factors and intrinsic antimicrobial activity were determined in cervicovaginal lavage samples collected on study days 0, 7, 14, and 21. RESULTS: No increase in pro-inflammatory cytokines was observed. Rather cytokines and protective factors including interleukin (IL)-1 receptor antagonist, immunoglobulins and human beta-defensin 2 were lower in the drug compared with the placebo group. All of the mediators returned towards baseline on day 21. Women who were cycling had lower levels of most proteins on study days 7 and/or 14 compared with women on oral contraceptives; however, the magnitude of decline was greater in women who received PRO 2000 compared with placebo gel. The reduction in protective factors was not associated with a loss in the intrinsic anti-viral (HIV or herpes simplex virus) activity or anti-bacterial activity (Escherichia coli or Staphylococcus aureus). CONCLUSION: In contrast to experience with nonoxynol-9, PRO 2000 did not trigger an inflammatory response in cervicovaginal secretions. There was a modest reduction in mucosal immune mediators, but this loss was not associated with a reduction in intrinsic antimicrobial activity.

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalAIDS
Volume21
Issue number4
DOIs
StatePublished - Feb 2007
Externally publishedYes

Fingerprint

Placebos
Cytokines
Nonoxynol
Gels
Defensins
Mucosal Immunity
Interleukin-1 Receptors
Therapeutic Irrigation
Simplexvirus
Oral Contraceptives
Anti-Infective Agents
Chemokines
Staphylococcus aureus
Immunoglobulins
HIV
Escherichia coli
PRO 2000
Infection
Pharmaceutical Preparations
Protective Factors

Keywords

  • Cytokines
  • Defensins
  • Genital herpes
  • HIV
  • Innate immunity
  • Microbicides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity. / Keller, Marla J.; Guzman, Esmeralda; Hazrati, Ehsan; Kasowitz, Andrea; Cheshenko, Natalia V.; Wallenstein, Sylvan; Cole, Amy L.; Cole, Alexander M.; Profy, Albert T.; Wira, Charles R.; Hogarty, Kathleen; Herold, Betsy.

In: AIDS, Vol. 21, No. 4, 02.2007, p. 467-476.

Research output: Contribution to journalArticle

Keller, MJ, Guzman, E, Hazrati, E, Kasowitz, A, Cheshenko, NV, Wallenstein, S, Cole, AL, Cole, AM, Profy, AT, Wira, CR, Hogarty, K & Herold, B 2007, 'PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity', AIDS, vol. 21, no. 4, pp. 467-476. https://doi.org/10.1097/QAD.0b013e328013d9b5
Keller, Marla J. ; Guzman, Esmeralda ; Hazrati, Ehsan ; Kasowitz, Andrea ; Cheshenko, Natalia V. ; Wallenstein, Sylvan ; Cole, Amy L. ; Cole, Alexander M. ; Profy, Albert T. ; Wira, Charles R. ; Hogarty, Kathleen ; Herold, Betsy. / PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity. In: AIDS. 2007 ; Vol. 21, No. 4. pp. 467-476.
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AU - Keller, Marla J.

AU - Guzman, Esmeralda

AU - Hazrati, Ehsan

AU - Kasowitz, Andrea

AU - Cheshenko, Natalia V.

AU - Wallenstein, Sylvan

AU - Cole, Amy L.

AU - Cole, Alexander M.

AU - Profy, Albert T.

AU - Wira, Charles R.

AU - Hogarty, Kathleen

AU - Herold, Betsy

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N2 - OBJECTIVE: Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective of this study was to examine the effect of 14 daily applications of 0.5% PRO 2000 or placebo gel on mediators of mucosal immunity and intrinsic antimicrobial activity. DESIGN AND METHODS: A randomized, prospective, double-blind, placebo-controlled study was conducted among 24 healthy, abstinent women. Levels of cytokines, chemokines, defensins, and other protective factors and intrinsic antimicrobial activity were determined in cervicovaginal lavage samples collected on study days 0, 7, 14, and 21. RESULTS: No increase in pro-inflammatory cytokines was observed. Rather cytokines and protective factors including interleukin (IL)-1 receptor antagonist, immunoglobulins and human beta-defensin 2 were lower in the drug compared with the placebo group. All of the mediators returned towards baseline on day 21. Women who were cycling had lower levels of most proteins on study days 7 and/or 14 compared with women on oral contraceptives; however, the magnitude of decline was greater in women who received PRO 2000 compared with placebo gel. The reduction in protective factors was not associated with a loss in the intrinsic anti-viral (HIV or herpes simplex virus) activity or anti-bacterial activity (Escherichia coli or Staphylococcus aureus). CONCLUSION: In contrast to experience with nonoxynol-9, PRO 2000 did not trigger an inflammatory response in cervicovaginal secretions. There was a modest reduction in mucosal immune mediators, but this loss was not associated with a reduction in intrinsic antimicrobial activity.

AB - OBJECTIVE: Vaginal microbicides should protect against infection without disrupting the mucosal environment or its mediators of host defense. The objective of this study was to examine the effect of 14 daily applications of 0.5% PRO 2000 or placebo gel on mediators of mucosal immunity and intrinsic antimicrobial activity. DESIGN AND METHODS: A randomized, prospective, double-blind, placebo-controlled study was conducted among 24 healthy, abstinent women. Levels of cytokines, chemokines, defensins, and other protective factors and intrinsic antimicrobial activity were determined in cervicovaginal lavage samples collected on study days 0, 7, 14, and 21. RESULTS: No increase in pro-inflammatory cytokines was observed. Rather cytokines and protective factors including interleukin (IL)-1 receptor antagonist, immunoglobulins and human beta-defensin 2 were lower in the drug compared with the placebo group. All of the mediators returned towards baseline on day 21. Women who were cycling had lower levels of most proteins on study days 7 and/or 14 compared with women on oral contraceptives; however, the magnitude of decline was greater in women who received PRO 2000 compared with placebo gel. The reduction in protective factors was not associated with a loss in the intrinsic anti-viral (HIV or herpes simplex virus) activity or anti-bacterial activity (Escherichia coli or Staphylococcus aureus). CONCLUSION: In contrast to experience with nonoxynol-9, PRO 2000 did not trigger an inflammatory response in cervicovaginal secretions. There was a modest reduction in mucosal immune mediators, but this loss was not associated with a reduction in intrinsic antimicrobial activity.

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