BACKGROUND: Interleukin (IL)-18 is a potent immunomodulatory cytokine promoting TH-1 and cytotoxic immune responses through interferon (IFN)-gamma induction. The aim of this study was to investigate the production of IL-18 by squamous cell carcinoma of the head and neck (HNSCC). METHODS: The expression of IL-18 was analyzed by reverse transcriptase-polymerase chain reaction, Western blot, and ELISA in untreated and 5-fluorouracil (5-FU)-treated HNSCC cell lines. Immunohistochemical analysis was performed on tumor specimens from 16 patients with primary invasive HNSCC. RESULTS: We have demonstrated that HNSCC cell lines express IL-18 at the mRNA, as well as the protein, level. However, the IL-18 protein was expressed intracellularly and predominantly released as an unprocessed inactive 24-kDa form. After exposure to 5-FU, the processed form of IL-18 was detected in the supernatants of both HNSCC cell lines. CONCLUSIONS: These results indicate that HNSCC cells are a potential source of IL-18 cytokine. The finding that the exposure to 5-FU can elicit its processing suggests a novel target for immunomodulatory intervention in patients with HNSCC. Copyright 2004 Wiley Periodicals, Inc. Head Neck 26: 494-503, 2004
BACKGROUND:Interleukin (IL)-18 is a potent immunomodulatory cytokine promoting TH-1 and cytotoxic immune responses through interferon (IFN)-gamma induction. The aim of this study was to investigate the production of IL-18 by squamous cell carcinoma of the head and neck (HNSCC). METHODS: The expression of IL-18 was analyzed by reverse transcriptase-polymerase chain reaction, Western blot, and ELISA in untreated and 5-fluorouracil (5-FU)-treated HNSCC cell lines. Immunohistochemical analysis was performed on tumor specimens from 16 patients with primary invasive HNSCC. RESULTS: We have demonstrated that HNSCC cell lines express IL-18 at the mRNA, as well as the protein, level. However, the IL-18 protein was expressed intracellularly and predominantly released as an unprocessed inactive 24-kDa form. After exposure to 5-FU, the processed form of IL-18 was detected in the supernatants of both HNSCC cell lines. CONCLUSIONS: These results indicate that HNSCC cells are a potential source of IL-18 cytokine. The finding that the exposure to 5-FU can elicit its processing suggests a novel target for immunomodulatory intervention in patients with HNSCC. Copyright 2004 Wiley Periodicals, Inc. Head Neck 26: 494-503, 2004