Brackowski R, Zubelewicz B, Romanowski W, Lissoni P, Barni S, Tancini G, Maestroni G J
Silesian University School of Medicine, Bytom, Poland.
J Biol Regul Homeost Agents. 1994 Jul-Sep;8(3):77-80.
Previous experimental studies have suggested the possibility to modulate the biological activity and toxicity of cytokines by immunomodulating neurohormones. In particular, the pineal hormone melatonin (MLT) has been proven to amplify the immune effects of IL-2 and to reduce its toxicity. On this basis, we decided to investigate the effect of MLT on biological activity and toxicity of another important antitumor cytokine, TNF. The study was performed in 14 metastatic solid tumor patients, for whom no effective standard antitumor therapy was available. Informed consent was previously obtained from each patient. Patients were randomized to be treated with TNF or TNF plus MLT. Recombinant human TNF was given at a daily dose of 0.75 mg intravenously for 5 consecutive days. MLT was given orally at a daily dose of 40 mg, starting 7 days before TNF. Lymphocyte mean number observed at the end of TNF infusion was significantly higher in patients treated with TNF plus MLT than in those receiving TNF alone. On the contrary, no significant difference occurred in hemoglobin, platelet and neutrophil mean values. Asthenia and hypotension were significantly less frequent in patients treated with TNF plus MLT, whereas no difference occurred in the frequency of fever and chills. Even though limited to a small number of patients, this preliminary study would suggest the possibility to modulate TNF toxicity and biological activity by a concomitant treatment with the pineal hormone MLT.
以往的实验研究表明，通过免疫调节神经激素来调节细胞因子的生物活性和毒性是有可能的。特别是，松果体激素褪黑素（MLT）已被证明可增强白细胞介素-2的免疫效应并降低其毒性。在此基础上，我们决定研究MLT对另一种重要的抗肿瘤细胞因子肿瘤坏死因子（TNF）的生物活性和毒性的影响。该研究在14例转移性实体瘤患者中进行，这些患者没有有效的标准抗肿瘤治疗方法。事先已获得每位患者的知情同意。患者被随机分为接受TNF治疗或TNF加MLT治疗。重组人TNF以每日0.75毫克的剂量静脉注射，连续5天。MLT以每日40毫克的剂量口服，在TNF治疗前7天开始服用。在TNF输注结束时观察到，接受TNF加MLT治疗的患者的淋巴细胞平均数显著高于单独接受TNF治疗的患者。相反，血红蛋白、血小板和中性粒细胞的平均值没有显著差异。接受TNF加MLT治疗的患者中，乏力和低血压的发生率显著较低，而发热和寒战的发生率没有差异。尽管该研究仅限于少数患者，但这项初步研究表明，通过与松果体激素MLT联合治疗来调节TNF毒性和生物活性是有可能的。
