Polson R J, Bomford A, Berry H, Williams R
Liver Unit, King's College Hospital, London.
Ann Rheum Dis. 1988 Jul;47(7):570-5. doi: 10.1136/ard.47.7.570.
The response of peripheral blood lymphocytes to stimulation by mitogens such as phytohaemagglutinin (PHA) is commonly depressed in both rheumatoid arthritis and iron deficiency, and as many rheumatoid patients are anaemic with evidence of abnormal iron metabolism it is possible that the same mechanism underlies the observed suppression in both conditions. In the present study the mitogenic response to PHA of lymphocytes from three rheumatoid patients, who were also iron deficient, and two healthy controls has been shown to be significantly less in iron deficient than iron containing media (p less than 0.001). In addition, iron deficient sera from these patients reduced the PHA induced proliferation of lymphocytes from a normal subject (p less than 0.01), an effect which was prevented by prior addition of iron to these serum samples. In iron containing media lymphocytes from five patients and two controls showed no difference in their response to PHA for both the minimum mitogen concentration which enhanced transformation and the peak [3H]thymidine uptake; but patients' lymphocytes showed significantly less response to PHA concentrations of 5 and 10 mg/l (p less than 0.02), resulting in a reduction in the area under the dose response curves up to 20 mg/l (p less than 0.05). These findings show both that iron deficient sera can impair PHA induced lymphocyte transformation and that lymphocytes from iron deficient rheumatoid patients have impaired responsiveness to PHA. Iron is known to be required intracellularly for the enzyme ribonucleotide reductase, which is important for DNA synthesis, and reduced activity of this enzyme could explain these observed effects.
在类风湿性关节炎和缺铁状态下,外周血淋巴细胞对诸如植物血凝素(PHA)等有丝分裂原刺激的反应通常会受到抑制。由于许多类风湿患者贫血且有铁代谢异常的证据,所以有可能在这两种情况下观察到的抑制现象是由相同的机制引起的。在本研究中,已表明来自三名同时缺铁的类风湿患者和两名健康对照者的淋巴细胞,在缺铁培养基中对PHA的有丝分裂反应明显低于含铁血培养基(p<0.001)。此外,这些患者的缺铁血清降低了正常受试者淋巴细胞的PHA诱导增殖(p<0.01),预先向这些血清样本中添加铁可防止这种效应。在含铁血培养基中,五名患者和两名对照者的淋巴细胞对PHA的反应在增强转化的最低有丝分裂原浓度和[3H]胸腺嘧啶核苷摄取峰值方面没有差异;但患者的淋巴细胞对5和10mg/l的PHA浓度反应明显较低(p<0.02),导致剂量反应曲线下至20mg/l的面积减少(p<0.05)。这些发现表明,缺铁血清可损害PHA诱导的淋巴细胞转化,并且缺铁类风湿患者的淋巴细胞对PHA的反应性受损。已知细胞内的核糖核苷酸还原酶需要铁,该酶对DNA合成很重要,其活性降低可以解释这些观察到的效应。