Fluoride-induced interleukin-6 and interleukin-8 synthesis in human epithelial lung cells

Exposure to fluorides has been associated with asthmatic symptoms among wor kers in the aluminium industry. In a recent experimental study hydrogen flu oride (HF) was found to induce a weak inflammatory response in humans. In t he present study the potential of sodium fluoride (NaF) and HF to induce cy tokine response was examined and ho tv these responses are modulated by Al3 + in a human epithelial lung cell line (A549). Dose-response experiments sh owed a maximal release of IL-6 and IL-8 at a concentration of 5 mM NaF 24 h after addition. The responses to HF were of a similar magnitude as for NaF , Time-course experiments shelved a NaF-induced IL-6 response at 5 h, where as an IL-8 response was observed after 10 h. Cycloheximide treatment comple tely abolished the NaF-induced cytokine responses. A marked increase in the mRNA level for IL-6 was observed already 2 h after exposure to 5 mM NaF, a nd presumably is a prerequisite for the subsequent increase of IL-6. The fl uoride-induced effects on IL-6 and IL-8 release were strongly reduced by pr etreatment with deferoxamine (an Al3+-chelator), and enhanced by addition o f Al3+. This indicates that an AlF4--complex, a known activator of GTP-bind ing proteins, is involved in fluoride-induced IL-6 and IL-8 responses in A5 49 cells.