Effects of Taxol on TNF-α and IL-6 Production by Human Peripheral Blood Cells

Taxol, a new drug isolated from the bark of the Pacific yew tree, is being used in treating patients with breast, ovary, lung, neck, and brain cancer.’.* The therapeutic mechanisms of taxol are not yet completely known. Taxol binds to p-tubulin, stabilizes microtubules against dep~lymerization,~ and interferes with microtubules during the cell divisions, blocking the cell through me tapha~e .~ Probably, microtubules are not the only targets of this drug. On murine macrophages, taxol appears to have an action similar to that of bacterial lipopolysaccharide (LPS). There is some evidence that the drug binds to receptors proximal to those of LPS.’ LPS activates antitumor mechanisms such as biosynthesis of tumor necrosis factor alpha (TNF-cY)~,~ and direct macrophage tumoricidal activity.8 Thus, the antitumor activities of taxol may be in part related to its ability to stimulate macrophages. The objective of this study was to determine if cells from the peripheral blood of healthy donors or tumor patients can be stimulated with taxol to produce TNF-a or IL-6 directly or in the presence of “priming” signals, such as those provided by interferon-gamma (IFN-y).