Interleukin‐18 Inhibition of Oral Carcinoma Cell Proliferation

Nilkaeo, A.; Bhuvanath, S.

Interleukin‐18 (IL‐18), a pro‐inflammatory cytokine that is produced by both lymphoid and nonlymphoid cells, has a critical role in modulation of innate and adaptive immunity. Its primary function in stimulation of IFN‐γ production and stimulation of NK‐cell‐cytotoxic activities makes this cytokine a candidate for cancer immunotherapy. In oral cavity, this cytokine is produced by oral epithelia and carcinoma cells and is related to tumour regression in nude mice bearing salivary adenocarcinoma. However, direct effects of this cytokine on oral cancer cells have not been elucidated. In this project, we investigated IL‐18 effect on an oral carcinoma (KB) cell line. With RT‐PCR technique, KB‐cell line was found to express IL‐18 receptors (IL‐18Rα and IL‐18Rβ), indicating that this oral carcinoma line is a target for IL‐18 study. We showed that recombinant human IL‐18 inhibited KB‐cell proliferation by 17% at concentration of 100 ng/ml (P < 0.05), whereas LDH release by these cells in treatment group and control groups was comparable, indicating that IL‐18 suppression of cell proliferation was not mediated by the induction of cell death. To further address this hypothesis, we found that IL‐18 treatment did not induce apoptotic cell death, as studied by DNA laddering and TUNEL assays. In addition, expression pattern of cell death‐controlling genes (bcl‐2 and bax) was not altered by this cytokine. Findings in these studies indicated that suppression of KB‐cell proliferation may be attributed to control of cell cycle, growth arrest or induction of cell differentiation. The data presented in this project could provide an insight of how cancer cell directly responds to IL‐18, as this cytokine is an important regulator of anticancer mechanisms.