Lung Bleomycin Fibrosis

Bleomycin is an antibiotic used to treat a number of cancers including squamous cell carcinoma of the esophagus, head, neck and cervix, as well as both Hodgkin and non-Hodgkin lymphoma. The major constraint to successful treatment outcomes with bleomycin is its potential to induce interstitial pulmonary fibrosis (IPF) in up to 10% of patients.

In murines, bleomycin administration induces a similar pulmonary condition that is characterized by the infiltration of leukocytes, fibroblast proliferation and an increase in collagen within lung tissue. C57BL/6 mice are prone to the toxic fibrotic effects of bleomycin and are a good model for screening compounds in the treatment of bleomycin-induced IPF.

Category(s)

Preclinical Drug Efficacy Studies

Species

Mice (C57BL/6, Female, 8-10 weeks)

Basic Methodology

After an initial acclimation period, animals are given an injection of bleomycin via intratracheal instillation on study Day 1. Body weights are collected 2X/week and on Day 28, animals are anesthetized with an Isoflurane/O2 mixture, and bled via the retro-orbital sinus. Tissues and BAL fluid are also collected. Compound dosing follows the study protocol.

Measurements

Clinical observations, body weight (2X/week), serum assay of cytokines using Luminex XMAP, homogenization of tissue for the assay of cytokines using ELISA and Luminex XMAP, FFPE remaining tissues for histological examination of collagen and fibrin deposition, lung assessment using Buxco plethysmograph system.

Literature References:

Jules-Elysie K, White DA. (1990) Bleomycin-induced pulmonary toxicity. Clin Chest Med; 11:1.

Meadors M, Floyd J, Perry MC. (2006) Pulmonary toxicity of chemotherapy. Semin Oncology; 33:98.