Cooper Angela, Mikhail Ashraf, Lethbridge Mark W, Kemeny D Michael, Macdougall Iain C
Department of Renal Medicine, GKT School of Medicine, King's College Hospital, London, United Kingdom.
J Am Soc Nephrol. 2004 Jul;15(7):1877-82. doi: 10.1097/01.asn.0000131523.17045.56.
It was hypothesized that pentoxifylline might improve the response to recombinant human erythropoietin (rh-Epo) in anemic renal failure patients. Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin of <10.7 g/dl for 6 mo before treatment and a rh-Epo dose of > or =12,000 IU/wk, were recruited. They were treated with oral pentoxifylline 400 mg o.d. for 4 mo. Ex vivo T cell generation of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) from the patients was assessed before treatment and 6 to 8 wk after therapy. A total of 12 of 16 patients completed the study. Before therapy, the 12 patients' mean hemoglobin concentration was 9.5 +/- 0.9 g/dl. After 4 mo of pentoxifylline treatment, the mean hemoglobin concentration increased to 11.7 +/- 1.0 g/dl (P = 0.0001). Baseline ex vivo T cell expression of TNF-alpha decreased from 58% +/- 11% to 31% +/- 23% (P = 0.0007) after therapy. Likewise, IFN-gamma expression decreased from 31% +/- 10% to 13% +/- 10% (P = 0.0002). Pentoxifylline therapy may significantly improve the hemoglobin response in patients with previously rh-Epo-resistant anemia in renal failure. This may occur due to inhibition of proinflammatory cytokine production, which could interfere with the effectiveness of rh-Epo.
研究假设己酮可可碱可能会改善贫血性肾衰竭患者对重组人促红细胞生成素（rh-Epo）的反应。招募了16例终末期肾病（ESRD）且对rh-Epo耐药性贫血的患者，其定义为治疗前6个月血红蛋白<10.7 g/dl且rh-Epo剂量≥12,000 IU/周。他们接受口服己酮可可碱400 mg每日一次，共4个月。在治疗前以及治疗后6至8周评估患者肿瘤坏死因子α（TNF-α）和干扰素γ（IFN-γ）的体外T细胞生成情况。16例患者中有12例完成了研究。治疗前，这12例患者的平均血红蛋白浓度为9.5±0.9 g/dl。己酮可可碱治疗4个月后，平均血红蛋白浓度升至11.7±1.0 g/dl（P = 0.0001）。治疗后，TNF-α的基线体外T细胞表达从58%±11%降至31%±23%（P = 0.0007）。同样，IFN-γ表达从31%±10%降至13%±10%（P = 0.0002）。己酮可可碱治疗可能会显著改善先前对rh-Epo耐药的肾衰竭贫血患者的血红蛋白反应。这可能是由于抑制了促炎细胞因子的产生，而促炎细胞因子可能会干扰rh-Epo的有效性。
