2023-11-302024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/653897當致病的抗原分子入侵生物體內時，體內的免疫細胞便會產生各種免疫反應抵御與排除這些致病因子，以維護身體健康。一般來說，免疫反應是良性且暫時的，但當抗原反覆入侵、或者免疫系統失控時，免疫反應便有可能反過來形成疾病傷害自身。因此，如何調節與控制免疫反應為一重要課題。藥物是最常見且傳統的免疫調控方式，但有著劑量、吸收率和副作用等問題，因此非藥物型的物理刺激目前已成為生醫學者對免疫調控的新研究目標。 在本計畫的研究中，我們仍會以脂多醣（Lipopolysaccharide，LPS）來誘發人類血液分泌炎性細胞因子，接著將前期計畫中開發用以抗癌和保護神經細胞的循環式熱療法（Thermal cycling-hyperthermia，TC-HT）使用在脂多醣刺激過的血液上，實驗發現TC-HT能夠有效抑制炎性細胞因子的分泌，而且效果比傳統連續熱療法（Hyperthermia，HT）來得更好。此外，我們更進一步將血液中的周邊血單核球細胞分離出來，同樣以脂多醣誘導發炎後再施以TC-HT和HT，結果也發現TC-HT不僅比起HT更能有效抑制炎性細胞因子分泌，並且對細胞活性所造成的影響小也更為安全。綜合而言，TC-HT是一個安全且更有效的免疫調節方法，因此在本計畫中，我們規劃將TC-HT此技術應用於人類單核球細胞株U-937所分化的巨噬細胞上，研究TC-HT除了能調節炎性細胞因子的分泌外，是否還有其他的免疫調節功能，諸如：促進吞噬作用、調節細胞遷移能力、改變趨化因子分泌等。除了TC-HT技術之外，我們也預計研究電場和電磁場等其他物理刺激是否也有調節免疫反應的功能，並深入至訊息傳遞路徑的層面探討這些物理刺激是藉由何種機制起到免疫調節的功能。 When pathogenic antigens invade, immune cells activate various immunological responses to resist and eliminate these pathogens in order to maintain health. The immune response is generally benign and temporary, but as the antigen repeatedly occurs or the immune system is out of control, the immune response may turn against normal tissues and cause disease. Therefore, immunomodulation is an important topic to study. Drugs are the most common and traditional way for immunomodulation, but the efficacy is constrained by drug dosage, absorption rate, and adverse effects. Therefore, some medical researchers have focused on physical stimuli as novel methods for immunomodulation to avoid the drawbacks of drugs. In this project, we also use lipopolysaccharide (LPS) to induce the secretion of inflammatory cytokines in human blood. The study finds that thermal cycling-hyperthermia (TC-HT) could effectively suppress the secretion of inflammatory cytokines, achieving better results than continuous hyperthermia (HT). In addition, we further isolate peripheral blood mononuclear cells (PBMCs) from the blood, and similarly induce inflammation on them via LPS. Then the PBMCs are treated with TC-HT and HT, and the results show that TC-HT not only exhibit a better anti-inflammatory effect than HT, but also has almost no influence on the PBMCs’ viabilities. Therefore, we believe that TC-HT is a safer and more effective method of immunomodulation than HT. In this project, we will continue to investigate other immunomodulatory effects of TC-HT, such as promoting phagocytosis and regulating cell migration and chemokine secretion, using an in vitro macrophage model differentiated from the human mononuclear cell line U-937. In addition to TC-HT technique, we will also apply other physical stimuli such as low-intensity pulsed electric field (LIPEF) and electromagnetic field to in vitro macrophage model to observe their immunomodulatory potentials. The activation of the regulation signalling pathways will be investigated as well, in order to elaborate how these physical stimuli achieve immunomodulation.免疫調節; 熱療法; 抗發炎; 物理刺激;Immunomodulation; hyperthermia; anti-inflammation; physical stimuli