Oral therapy with proteolytic enzymes decreases excessive TGF-β levels in human blood
Oral therapy with proteolytic enzymes decreases excessive TGF-β levels in human blood
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DOI：
10.1007/s002800170003
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发表时间：
2001-07-01
影响因子：
3
通讯作者：
Herbacek, I
中科院分区：
文献类型：
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作者：
Desser, L;Holomanova, D;Herbacek, I
口服蛋白水解酶 (OET) 与含有木瓜蛋白酶、菠萝蛋白酶、胰蛋白酶和胰凝乳蛋白酶的组合药物产品的治疗已被证明对临床环境有益，例如放疗引起的纤维化、博莱霉素肺毒性和癌症免疫抑制，目前已知所有这些都伴随着过度的转化生长因子-β (TGF-β) 产生。已经证明，蛋白水解酶通过将蛋白酶抑制剂α2巨球蛋白（α2M）从“慢”形式转化为“快”形式来降低血清中的TGF-β水平，由此“快”形式不可逆地结合并灭活TGF-β。在这项研究中，我们研究了 OET 对类风湿关节炎 (RA) (n = 38)、骨髓纤维化 (OMF) (n = 7) 和带状疱疹 (HZ) (n = 7) 患者血清中 TGF-β 浓度的影响。七十八名健康志愿者作为对照。通过酶联免疫吸附测定（ELISA）评估血清中的TGF-β水平。我们已经证明，在健康志愿者和患者中，血清中的活性和潜伏 TGF-β 之间存在相关性（r = 0.8021；P < 0.0001）。 OET 治疗对健康志愿者或 TGF-β 水平正常的患者的 TGF-β1 浓度没有显着影响。在 TGF-β1 浓度升高（> 50 ng/ml 血清）的患者中，OET 降低了 RA（P < 0.005）、OMF（P < 0.05）和 HZ（P < 0.05）中的 TGF-β1。结论：这些结果支持这样的观点：OET 对于部分以 TGF-1 过量产生为特征的疾病有益。
Therapy with oral proteolytic enzymes (OET) with combination drug products containing papain, bromelain, trypsin, and chymotrypsin has been shown to be beneficial in clinical settings such as radiotherapy-induced fibrosis, bleomycin pneumotoxicity and immunosuppression in cancer, all of which are nowadays known to be accompanied by excessive transforming growth factor-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha 2M) from the "slow" form into the "fast" form, whereby the "fast" form binds and inactivates TGF-beta irreversibly. In this study we have investigated the effect of OET on the concentration of TGF-beta in serum of patients with rheumatoid arthritis (RA) (n = 38), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and latent TGF-beta in serum (r = 0.8021; P < 0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or patients with a normal level of TGF-beta. In patients with elevated TGF-beta1 concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P < 0.005), in OMF (P < 0.05) and in HZ (P < 0.05). Conclusion: These results support the concept that OET is beneficial in diseases characterized in part by TGF-1 overproduction.