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題名 | Depressed Cytolytic Activity of Peripheral Blood Mononuclear Cells in Unusually High Paclitaxel Concentrations: Reversal by IL-2 and IL-12=第二與第十二介白質可恢復周邊血液單核細胞受高濃度太平洋紫杉醇抑制的細胞毒殺能力 |
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作者 | 陳育民; 楊文光; 丁兆治; 楊登美; 彭汪嘉康; 彭瑞鶻; | 書刊名 | 中華醫學雜誌 |
卷期 | 62:12 1999.12[民88.12] |
頁次 | 頁867-874 |
分類號 | 418.31 |
關鍵詞 | 細胞毒殺能力; 第二介白質; 第四介白質; 第十二介白質; 太平洋紫杉醇; Cytotoxicity; Interleukin-2; Interleukin-4; Interleukin-12; Paclitaxel; |
語文 | 英文(English) |
中文摘要 | 背景:人類淋巴球的功能會受高濃度的太平洋紫杉醇抑制,此種抑制清況可籍由使用第二介白質來改善。但是仍未有試驗利用人體藥物動力學來決定處理淋巴球的太平洋紫杉醇濃度,也未有試驗能明確其它細胞激素可否恢復受太平洋紫杉醇抑制的淋巴球之細胞毒殺能力。 方法:我們嘗試使用不同濃度的太平洋紫杉醇處理周邊血液單核細胞,從而評估其於不同時間後對K.562癌細胞的細胞毒殺能力。 結果:當使用類似太平洋紫杉醇的臨床治療劑量時,周邊血液單核細胞的細胞毒殺功能並未受抑制。而當太平洋紫杉醇的濃度增加10倍時,遇邊血液單核細胞的細胞毒殺能力則明顯下降。此種抑制情況是可藉看合併使用低劑量的第二或第十二介白質來恢復,但使用顆粒球吞噬球生戊素則未有幫助,而使用第四介白質則會使情況更糟。以第二或第十二介白質恢復單核細胞的細胞毒殺功能約需時48.72小時。 結論:結果顯示,當考慮投予病患高劑量太平洋紫杉醇時,應將藥物之投予時間延長,或合併使用低劑量的第二或第十二介白質,從而降低太平洋紫杉醇抑制單核細胞之細胞毒殺功能的能力。 |
英文摘要 | Background: Human lymphocyte function was inhibited by high concentrations of paclitaxel and the effect was reversed by interleukin (IL)-2. However, there was no parallel study determining the relationship between paclitaxel concentrations in the lymphocyte cultures and pharmacokinetic analysis in human patients, nor was there any study on the reversal by cytokines, other than IL-2, of the paclitaxel-induced suppression of lymphocyte cytotoxicity. Methods: We tested the effect of different doses of paclitaxel with various incubation times on the cytolytic activity of peripheral blood mononuclear cells (PBMNCS) against K-562 target cells. Results: Our results showed that using a schedule similar to that for treating patients with tolerable doses of paclitaxel, no inhibition of cytolytic activity of PBMNCs was seen. When the paclitaxel concentration was increased 10-fold, the cytolytic activity of PBMNCs was significantly reduced. This suppression was reversed by the simultaneous addition of a low dose (10 U/ml) of IL-2 or IL-12. Addition of granulocyte macrophage-colony stimulating factor (10 U/ml) did not affect the cytolytic activity of PBMNCS, whereas addition of IL-4 reduced it. Time kinetic studies revealed that, with the addition of IL-2 or IL-12, most of the mononuclear cellular cytolytic activity recovered within 48 to 72 hours. Conclusions: These findings suggested that, to reduce the toxicity on mononuclear cellular function when high-dose paclitaxel treatment is elected in clinical practice, paclitaxel should be infused over a longer duration of time, or the treatment should be combined with the administration of a low dose of IL-2 or IL-12. |
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