Imiquimod Injection to Rabbit Vocal Folds: A Preliminary, Preclinical Investigation

Stephanie Teng, Gregory R. Dion, Danielle N. Sin, Nao Hiwatashi, Peter A. Benedict, Milan R. Amin, Ryan C. Branski

Research output: Contribution to journalArticle

Abstract

Objective: Given the recalcitrant nature of recurrent respiratory papillomatosis, targeted therapies to reduce disease burden are fundamental to improved patient care paradigms. We seek to demonstrate the safety of imiquimod injection into vocal fold mucosa by evaluating the degree of laryngeal edema, histopathologic changes to vocal fold structure, and serologic interferon α (IFNα) levels following injection. Study Design: Preclinical. Setting: Academic institution. Subjects and Methods: Six New Zealand White rabbits underwent unilateral injection of 100 µg of sterile imiquimod (1 µg/µL), with 100 µL of normal saline injected into the contralateral vocal fold. Direct laryngoscopy was performed on days 3, 7, and 30 following injection. Larynges from 3 rabbits were harvested on postinjection day 7 for histologic analysis. The remaining 3 rabbit larynges were harvested on day 30. Serial serum samples were drawn for IFNα quantification via immunoassay. Results: No signs of respiratory distress were observed at any point. Vocal fold appearance was not clinically divergent between imiquimod and control conditions via serial direct laryngoscopic evaluation. No inflammatory lesions or scarring were identified following injection. Histology showed no signs of acute inflammatory processes or changes in the control or imiquimod injection groups. Serum IFNα increased at days 3 and 7 following imiquimod injection (P <.0001 and P =.0368, respectively), before returning to baseline by day 14. Conclusions: Vocal fold imiquimod injection did not result in notable morbidity in this preclinical model. However, serum IFNα concentrations increased transiently. These data are critical to advance the therapeutic utility of this compound, particularly in the setting of recurrent respiratory papillomatosis.

Original languageEnglish (US)
Pages (from-to)702-705
Number of pages4
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume156
Issue number4
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Fingerprint

imiquimod
Vocal Cords
Rabbits
Injections
Interferons
Larynx
Laryngeal Edema
Serum
Laryngoscopy
Immunoassay
Cicatrix
Histology
Patient Care
Mucous Membrane

Keywords

  • imiquimod
  • recurrent respiratory papillomatosis

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

Teng, S., Dion, G. R., Sin, D. N., Hiwatashi, N., Benedict, P. A., Amin, M. R., & Branski, R. C. (2017). Imiquimod Injection to Rabbit Vocal Folds: A Preliminary, Preclinical Investigation. Otolaryngology - Head and Neck Surgery (United States), 156(4), 702-705. https://doi.org/10.1177/0194599816689585

Imiquimod Injection to Rabbit Vocal Folds : A Preliminary, Preclinical Investigation. / Teng, Stephanie; Dion, Gregory R.; Sin, Danielle N.; Hiwatashi, Nao; Benedict, Peter A.; Amin, Milan R.; Branski, Ryan C.

In: Otolaryngology - Head and Neck Surgery (United States), Vol. 156, No. 4, 01.04.2017, p. 702-705.

Research output: Contribution to journalArticle

Teng, S, Dion, GR, Sin, DN, Hiwatashi, N, Benedict, PA, Amin, MR & Branski, RC 2017, 'Imiquimod Injection to Rabbit Vocal Folds: A Preliminary, Preclinical Investigation', Otolaryngology - Head and Neck Surgery (United States), vol. 156, no. 4, pp. 702-705. https://doi.org/10.1177/0194599816689585
Teng, Stephanie ; Dion, Gregory R. ; Sin, Danielle N. ; Hiwatashi, Nao ; Benedict, Peter A. ; Amin, Milan R. ; Branski, Ryan C. / Imiquimod Injection to Rabbit Vocal Folds : A Preliminary, Preclinical Investigation. In: Otolaryngology - Head and Neck Surgery (United States). 2017 ; Vol. 156, No. 4. pp. 702-705.
@article{1e5fef60338b4333be8c965a9ea2a06e,
title = "Imiquimod Injection to Rabbit Vocal Folds: A Preliminary, Preclinical Investigation",
abstract = "Objective: Given the recalcitrant nature of recurrent respiratory papillomatosis, targeted therapies to reduce disease burden are fundamental to improved patient care paradigms. We seek to demonstrate the safety of imiquimod injection into vocal fold mucosa by evaluating the degree of laryngeal edema, histopathologic changes to vocal fold structure, and serologic interferon α (IFNα) levels following injection. Study Design: Preclinical. Setting: Academic institution. Subjects and Methods: Six New Zealand White rabbits underwent unilateral injection of 100 µg of sterile imiquimod (1 µg/µL), with 100 µL of normal saline injected into the contralateral vocal fold. Direct laryngoscopy was performed on days 3, 7, and 30 following injection. Larynges from 3 rabbits were harvested on postinjection day 7 for histologic analysis. The remaining 3 rabbit larynges were harvested on day 30. Serial serum samples were drawn for IFNα quantification via immunoassay. Results: No signs of respiratory distress were observed at any point. Vocal fold appearance was not clinically divergent between imiquimod and control conditions via serial direct laryngoscopic evaluation. No inflammatory lesions or scarring were identified following injection. Histology showed no signs of acute inflammatory processes or changes in the control or imiquimod injection groups. Serum IFNα increased at days 3 and 7 following imiquimod injection (P <.0001 and P =.0368, respectively), before returning to baseline by day 14. Conclusions: Vocal fold imiquimod injection did not result in notable morbidity in this preclinical model. However, serum IFNα concentrations increased transiently. These data are critical to advance the therapeutic utility of this compound, particularly in the setting of recurrent respiratory papillomatosis.",
keywords = "imiquimod, recurrent respiratory papillomatosis",
author = "Stephanie Teng and Dion, {Gregory R.} and Sin, {Danielle N.} and Nao Hiwatashi and Benedict, {Peter A.} and Amin, {Milan R.} and Branski, {Ryan C.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1177/0194599816689585",
language = "English (US)",
volume = "156",
pages = "702--705",
journal = "Otolaryngology - Head and Neck Surgery (United States)",
issn = "0194-5998",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Imiquimod Injection to Rabbit Vocal Folds

T2 - A Preliminary, Preclinical Investigation

AU - Teng, Stephanie

AU - Dion, Gregory R.

AU - Sin, Danielle N.

AU - Hiwatashi, Nao

AU - Benedict, Peter A.

AU - Amin, Milan R.

AU - Branski, Ryan C.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Objective: Given the recalcitrant nature of recurrent respiratory papillomatosis, targeted therapies to reduce disease burden are fundamental to improved patient care paradigms. We seek to demonstrate the safety of imiquimod injection into vocal fold mucosa by evaluating the degree of laryngeal edema, histopathologic changes to vocal fold structure, and serologic interferon α (IFNα) levels following injection. Study Design: Preclinical. Setting: Academic institution. Subjects and Methods: Six New Zealand White rabbits underwent unilateral injection of 100 µg of sterile imiquimod (1 µg/µL), with 100 µL of normal saline injected into the contralateral vocal fold. Direct laryngoscopy was performed on days 3, 7, and 30 following injection. Larynges from 3 rabbits were harvested on postinjection day 7 for histologic analysis. The remaining 3 rabbit larynges were harvested on day 30. Serial serum samples were drawn for IFNα quantification via immunoassay. Results: No signs of respiratory distress were observed at any point. Vocal fold appearance was not clinically divergent between imiquimod and control conditions via serial direct laryngoscopic evaluation. No inflammatory lesions or scarring were identified following injection. Histology showed no signs of acute inflammatory processes or changes in the control or imiquimod injection groups. Serum IFNα increased at days 3 and 7 following imiquimod injection (P <.0001 and P =.0368, respectively), before returning to baseline by day 14. Conclusions: Vocal fold imiquimod injection did not result in notable morbidity in this preclinical model. However, serum IFNα concentrations increased transiently. These data are critical to advance the therapeutic utility of this compound, particularly in the setting of recurrent respiratory papillomatosis.

AB - Objective: Given the recalcitrant nature of recurrent respiratory papillomatosis, targeted therapies to reduce disease burden are fundamental to improved patient care paradigms. We seek to demonstrate the safety of imiquimod injection into vocal fold mucosa by evaluating the degree of laryngeal edema, histopathologic changes to vocal fold structure, and serologic interferon α (IFNα) levels following injection. Study Design: Preclinical. Setting: Academic institution. Subjects and Methods: Six New Zealand White rabbits underwent unilateral injection of 100 µg of sterile imiquimod (1 µg/µL), with 100 µL of normal saline injected into the contralateral vocal fold. Direct laryngoscopy was performed on days 3, 7, and 30 following injection. Larynges from 3 rabbits were harvested on postinjection day 7 for histologic analysis. The remaining 3 rabbit larynges were harvested on day 30. Serial serum samples were drawn for IFNα quantification via immunoassay. Results: No signs of respiratory distress were observed at any point. Vocal fold appearance was not clinically divergent between imiquimod and control conditions via serial direct laryngoscopic evaluation. No inflammatory lesions or scarring were identified following injection. Histology showed no signs of acute inflammatory processes or changes in the control or imiquimod injection groups. Serum IFNα increased at days 3 and 7 following imiquimod injection (P <.0001 and P =.0368, respectively), before returning to baseline by day 14. Conclusions: Vocal fold imiquimod injection did not result in notable morbidity in this preclinical model. However, serum IFNα concentrations increased transiently. These data are critical to advance the therapeutic utility of this compound, particularly in the setting of recurrent respiratory papillomatosis.

KW - imiquimod

KW - recurrent respiratory papillomatosis

UR - http://www.scopus.com/inward/record.url?scp=85018993349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018993349&partnerID=8YFLogxK

U2 - 10.1177/0194599816689585

DO - 10.1177/0194599816689585

M3 - Article

C2 - 28171734

AN - SCOPUS:85018993349

VL - 156

SP - 702

EP - 705

JO - Otolaryngology - Head and Neck Surgery (United States)

JF - Otolaryngology - Head and Neck Surgery (United States)

SN - 0194-5998

IS - 4

ER -