EFFECTS OF PACLITAXEL ON CYTOKINE SYNTHESIS BY UNPRIMED HUMAN MONOCYTES, T-LYMPHOCYTES, AND BREAST-CANCER CELLS

Paclitaxel or Taxol has attracted a great deal of attention in recent years because of its immense success as a chemotherapeutic agent for n umerous types of cancer. It is known that paclitaxel stabilizes microt ubules, and this characteristic is the presumed primary mechanism for its antitumor activity. Recently, however, paclitaxel's ability to reg ulate gene expression, particularly in the murine system, has been rep orted by several groups. Here, we present research examining paclitaxe l's ability to alter expression of the interleukin-1 beta (IL-1 beta) and IL-8 cytokines in primary human monocytes, T lymphocytes, and four human breast cancer cell lines: MCF-7, ZR-75-1, MDA-MB-468, and MDA-M B-231. This report shows for the first time that treatment with 5-50 m u M paclitaxel increases steady-state levels of IL-1 beta mRNA in unpr imed human monocytes, MCF-7, and ZR-75-1 cells. Monocytes from eight d onors in 16 experiments showed increased IL-1 beta secretion upon trea tment; however, the increase in IL-1 beta production by monocytes was predicated on culturing in the absence of fetal bovine serum or in the presence of autologous human serum. In contrast to the IL-1 beta resu lts, paclitaxel did not have significant effects on IL-8 expression by monocytes, T lymphocytes, or the breast cancer cells. These data show a specific effect of paclitaxel on cytokine synthesis by both immune cells and cancer cells.