Ho A D, Männel D N, Wulf G, Kirchner H, Gundt A, Trede I, Rensch K, Hunstein W
Department of Internal Medicine and Poliklinik, University of Heidelberg, F.R.G.
Leukemia. 1990 Aug;4(8):584-9.
Deoxycoformycin (DCF) has been reported to cause immediate reduction and dysfunction of T lymphocytes, but the long-term effects on immune functions are still not known. As cytokine production is regulated by T helper-inducer lymphocytes and might represent a parameter for functional integrity of immunocompetent cells, we have measured the production of interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferons (IFN) by peripheral mononuclear cells (PMNC) from 10 patients with hairy cell leukemia 11-24 months after end of therapy with DCF. The patients were in continuous remission at the time of study. Despite an absolute reduction in CD3+ and CD4+ lymphocytes. there were no significant differences in IL-2 or TNF release between patients and controls. Except for a significant reduction in IFN-alpha release stimulated by Newcastle disease virus (NDV), IFN productions induced by other mitogens (phytohemagglutinin, PHA; Concanavalin A, ConA; pokeweed mitogen, PWM) and viral antigens were within normal range. There was also a decrease in proliferative responsiveness to PHA, but responses to ConA, PWM, and other viral antigens were normal. In five of the patients, we have monitored closely the changes in IL-2, TNF, and IFN before, during, and after treatment and could demonstrate a rapid normalization of initially decreased IL-2 release in all cases and also of TNF if the initial production was reduced. This study shows that, even though the absolute number of T lymphocytes and helper cells are reduced in the long-term observation after DCF treatment, the capacity to produce IL-2, TNF, and IFN-gamma was within normal range. Parallel to this observation, no opportunistic infections or frequency of infectious complications occurred in these patients.
据报道，脱氧助间型霉素（DCF）可导致T淋巴细胞立即减少并功能失调，但对免疫功能的长期影响仍不清楚。由于细胞因子的产生受辅助性诱导T淋巴细胞调节，并且可能代表免疫活性细胞功能完整性的一个参数，我们检测了10例毛细胞白血病患者在接受DCF治疗结束后11 - 24个月外周血单个核细胞（PMNC）产生白细胞介素-2（IL-2）、肿瘤坏死因子（TNF）和干扰素（IFN）的情况。研究时这些患者处于持续缓解状态。尽管CD3 +和CD4 +淋巴细胞绝对数量减少，但患者与对照组之间IL-2或TNF的释放没有显著差异。除了新城疫病毒（NDV）刺激引起的IFN-α释放显著减少外，其他有丝分裂原（植物血凝素，PHA；刀豆球蛋白A，ConA；商陆有丝分裂原，PWM）和病毒抗原诱导的IFN产生均在正常范围内。对PHA的增殖反应性也有所降低，但对ConA、PWM和其他病毒抗原的反应正常。我们对其中5例患者在治疗前、治疗期间和治疗后密切监测了IL-2、TNF和IFN的变化，结果表明，所有病例中最初降低的IL-2释放均迅速恢复正常，若最初TNF产生减少也可恢复正常。本研究表明，尽管在DCF治疗后的长期观察中T淋巴细胞和辅助细胞的绝对数量减少，但产生IL-2、TNF和IFN-γ的能力仍在正常范围内。与此观察结果一致的是，这些患者未发生机会性感染或感染并发症的频率增加。
