Induction of interleukin-1 and tumor necrosis factor by 12-O-tetradecanoylphorbol-13-acetate in phorbol ester-sensitive (SENCAR) and resistant (B6C3F1) mice.

12-O-tetradecanoylphorbol-13-acetate (TPA), the most potent skin tumor promoter known, evokes significant inflammatory responses in mouse skin after topical application. Infiltrating inflammatory cells have been hypothesized to contribute to genetic damage in epidermal cells through the generation of reactive oxygen intermediates (ROIs), thus facilitating the development of tumors. Interleukin-1 (IL-1) and tumor necrosis factor (TNF), small mol. wt cytokines produced by macrophages (MPs), are known to have important roles in the inflammatory process. Lipopolysaccharide (LPS)-triggered release of IL-1 and TNF was determined in culture supernatants of splenic MPs from phorbol ester-sensitive (SENCAR) and resistant (B6C3F1) mice following topical application of 8 micrograms of TPA twice in one week. The findings reported herein indicated that topical application of TPA primed splenic MPs from both SENCAR and B6C3F1 mice in a quantitatively similar manner for the production of IL-1 and TNF; in addition, the release of IL-1 and TNF by splenic MPs from control (naive or acetone-dosed) SENCAR and B6C3F1 mice in response to LPS-triggering in vitro was not significantly different. Therefore, the production and release of these cytokines by activated MPs does not correlate with the reported strain-dependent susceptibilities to TPA-induced inflammation and/or tumor promotion.