Oral mucositis is a frequent side-effect of
cancer therapy. A definitive method of prophylaxis or treatment is not yet available. As
pentoxifylline (PTX) and
thalidomide (TLD) have been shown to inhibit
cytokine synthesis, we studied the effects of these
cytokine inhibitors in an experimental
oral mucositis model.
Oral mucositis was induced in Golden hamsters by the administration of
5-fluorouracil (5-FU) followed by mechanical
trauma of the cheek pouch. On days 4, 5, 10, 12, 14 and 16, lesions induced by
5-FU were examined macroscopically and microscopically, and the presence and intensity of
hyperemia,
erythema,
edema, inflammatory cell infiltration, hemorrhagic areas,
ulcers and
abscesses were recorded. Saline (control), PTX (5, 15, 45 mg kg(-1)) or TLD (10, 30, 90 mg kg(-1)) were administered daily and animals were killed on day 10 for macroscopic and histological analysis and assay of
myeloperoxidase (MPO) activity. Animals were weighed daily, and total and differential leukocyte counts were performed on peripheral blood. PTX and TLD were found to reduce the macroscopic and histological parameters of
oral mucositis and MPO activity. PTX and TLD also reversed peripheral neutrophilia, but only PTX prevented
weight loss. The results indicate a protective effect of PTX and TLD, suggesting an important role for tumour
necrosis factor-alpha (
TNF-alpha) in the pathophysiology of
5-FU induced-
oral mucositis in hamsters.