Mucosal protection by cytokines

Oropharyngeal mucositis is a common, painful side effect seen in patients who receive aggressive chemotherapy, radiation, or both. Long thought to begin with direct epithelial cell damage, it now appears to be a complex process beginning in the submucosal endothelium and influenced by local cytokines. Previous attempts to use cytokines (including both topical and systemic transforming growth factor-beta, granulocyte- or granulocyte-macrophage colony-stimulating factors, and interleukin II) to prevent or treat mucositis were either inconclusive or, as in the case of interleukin II, associated with systemic toxicities. Recently palifermin (recombinant human keratinocyte growth factor, Kepivance [Amgen, Thousan Oaks, CA]) was approved as the first cytokine shown to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support. Several other potentially effective agents are in clinical trials. After 40 years of painful mucositis, relief for patients finally is in sight.