Local injections of corticotropin releasing factor reduce doxorubicin- induced acute inflammation in the eyelid

Linda Kirschen McLoon, Jonathan Wirtschafter

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Purpose. Doxorubicin chemomyectomy is an effective alternative treatment option for patients with blepharospasm and hemifacial spasm. One side effect of the use of doxorubicin in localized injections is the development of acute inflammation and skin injury at the injection site. Corticotropin releasing factor (CRF) was reported to reduce inflammation after acute inflammatory injuries due to other causes and at other sites. This study was performed to assess the potential CRF to prevent the development of skin injury and eyelid soreness after local doxorubicin injection. Methods. Rabbits received lower eyelid injections of either 75 or 150 μg CRF followed by injection of either 0.5, 1, or 2 mg doxorubicin or doxorubicin alone. Eyelids were assessed for changes in acute inflammatory by immunohistochemical localization of macrophages and monocytes using anti- CD11, an antibody specific for these cell types. Short-term alterations in vascular permeability were assessed using an Evans blue assay. Additional eyelids were followed daily for changes in the skin over the injection site to determine day of onset of skin injury and the total duration of skin injury. After 1 month, the eyelids were processed histologically for morphometric analysis of muscle fiber loss. Monkey eyelids also were examined for the effort of CRF and doxorubicin injections. Results. Doxorubicin alone produced an acute inflammatory reaction in the treated eyelids, with a large influx of macrophages monocytes throughout the connective tissue at 1 and 2 days. Corticotropin releasing factor pretreatment significantly reduced this influx of inflammatory cells into the connective tissue. Doxorubicin produced a large increase in vascular permeability in the treated eyelids, with resultant edema. Corticotropin releasing factor did not alter this change in vascular permeability, indicating that CRF appears to have a specific effect on migration of inflammatory cells rather than just a generalized effect on vascular permeability. Corticotropin releasing factor and doxorubicin cotreatments delayed the onset of skin injury and decreased the total duration of injury to the skin compared to doxorubicin alone. The effectiveness of doxorubicin chemomyectomy was maintained; muscle loss was significant at all does of CRF combined with doxorubicin. Conclusions. Corticotropin releasing factor dramatically decreased the acute inflammatory reaction that results in the eyelid from local doxorubicin injections. Not only did CRF reduce the acute influx of monocytes and macrophages, but it protected the skin overlying the injection site, substantially reducing the extent of skin injury. The efficacy of doxorubicin-induced muscle toxicity was maintained. A treatment protocol that combines myotoxicity with antiinflammatory activity in the treated eyelids may lead to a more effective patient treatment by increasing patient acceptance. The potential should be explored that CRF may be of clinical use in limiting tissue injury when administered immediately after extravasation during cancer chemotherapy.

Original languageEnglish (US)
Pages (from-to)834-841
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number5
StatePublished - 1997

Keywords

  • blepharospasm
  • corticotropin releasing factor
  • doxorubicin
  • hemifacial spasm
  • inflammation
  • myotoxicity
  • orbicularis oculi

Fingerprint Dive into the research topics of 'Local injections of corticotropin releasing factor reduce doxorubicin- induced acute inflammation in the eyelid'. Together they form a unique fingerprint.

Cite this