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Influence of Cefodizime on the Proliferative Response and the Cytokine Production by Human Mononuclear Cells

Cefodizme對人類週邊單核白血球增生反應及細胞素產生之影響

摘要


本研究應用增生反應和細胞素之產生,以探討Cefodizime對人類週邊單核白血球功能的影響。細胞增生反應是採用植物凝集素(Phytohemagglutinin)所誘發之淋巴球變形作用,Cefodizime劑量低於40μg/ml不會改變單核白血球增生反應,但當其劑量高達100μg/ml時,此增生反應會降低50%,Cefodizime本身於劑量1-100μg/ml範圍,對單核白血球並無任何增生分裂作用。細胞素之產生是以酵素結合兔疫吸附分析法(Enzyme-linked immunosorbent assay)加以評估, Cefodizime並不影響第一介白質(Interleukin-1),第二介白質(Interleukin -2),與干擾素γ(Interferon-γ)之產生。此外,經由流式細胞分析儀,偵測單核白血球細胞膜接受器之表現,Cefodizime亦不影響第二介白質接受器之表現。但在Cefodizime 100μg/ml處理下,腫瘤壞死因子α(Tumor necrosis factor-α)之產生要比Cefodizime劑量低於40μg/ml時為高。植物凝集素激化的單核白血球在培養24小時,其腫瘤壞死因子α的產生可達到最高(2300 pg/ml),但培養時間增長,其產量會隨之降低,例如在72小時則降為500pg/ml。但當加入Cefodizime100μg/ml共同培養,可促進腫瘤壞死因子α的產生,在培養24及72小時,分別為4200pg/ml與1200pg/ml。綜合這些結果,顯示出高劑量的Cefodizime能夠提高腫瘤壞死因子α的產生,但抑制植物擬集素激化單核白血球之增生反應。

並列摘要


Influence of cefodizime on the functions in vitro of human peripheral mononuclear leucocytes (MNL) was demonstrated by the proliferative response and by the cytokine production. The proliferative response was assayed by phytohemagglutinin (PHA)-induced lymphocyte transformation. The proliferative response by MNL did not change when cefodizime treatments were below 40μg/ml, but the response decreased by 50% when cefodizime treatment was up to 100μg/ml. Cefodizime itself, at the level of 1-100μg/ml, however, had no mitogenic effect on MNL. Determination of cytokine productions was performed by enzyme-linked immunosorbent assay. Interleukin-1, interleukin- 2 (IL - 2), and interferon - ï were shown no difference in production between the cefodizime- treated and-untreated groups. In addition, a flow cytometric analysis revealed no difference in the expression of membrane IL - 2 receptors on MNL between cefodizime-treated and - untreated groups, Production of tumor necrosis factor - alpha (TNF-X), however, was significantly higher at 100μg/ml of cefodizime treatment as compared with those treatments below 40μg/ml In the absence of cefodizime treatment, PHA-stimulated MNL had a maximum secretion of TNF-x (2300 pg/ml) at 24 - h cultivation, but the production of TNF-x decreased as the cultivated time prolonged, e.g. 500 pg/ml at 72 - h cultivation. On the other hand, when cocultivated with cefodizime at 100μg/ml, higher level of TNF-x, 4200 pg/ml and 1200pg/ml were obtained at 24-h and 72-h cultivation, respectively. These results indicate that higher dosages of cefodizime could enhance TNF-(X production but decrease the proliferative response by PHA-stimulated MNL.

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