Kimball P, Elswick R K, Shiffman M
Department of Surgery, Medical College of Virginia at the Virginia Commonwealth University, Richmond, VA 23838, USA.
J Med Virol. 2001 Nov;65(3):510-6.
Interferon is the primary treatment for hepatitis C virus (HCV). However, the long-term success rate is low particularly for African Americans relative to Caucasians and may be due to differential immune abilities. This study compared cytokine production from PHA-stimulated peripheral blood from 25 healthy and 40 HCV-infected African Americans and Caucasians. HCV patients were designated as IFN responders or nonresponders based on outcome after therapy. Ethnicity and genotype were associated with IFN response. IFN responders were 100% Caucasian, whereas nonresponders were 67% Caucasian and 33% African American (P = 0.01). Genotype 1 was present in 100% nonresponders and 50% responders (P < 0.05). Age, sex, liver histology, ALT, and viral titers were equivalent (ns). Cytokine production from healthy individuals showed ethnic variation in cytokine levels. Healthy African Americans produced greater amounts of IL-2 (P = 0.06), TNF-alpha (P = 0.06) and less IL-10 (P = 0.05) than healthy Caucasians. In contrast, IFN-gamma and TGF-beta levels were equivalent. Pretherapy cytokine production among HCV patients showed a similar pattern of ethnic variation. African American nonresponders produced more IL-2 (P = 0.06) and TNF-alpha (P = 0.02) than Caucasian nonresponders. Cytokine levels among Caucasian and African American nonresponders were equivalent (P = ns) to ethnically matched healthy individuals whereas Caucasian responders produced subnormal levels of IL-10 (P < 0.05) and TGF-beta (P < 0.05). Since all African Americans failed IFN therapy, cytokine production could not be compared with therapeutic outcome. However, comparison of cytokine production among Caucasians showed that responders produced less IL-10 (P < 0.001) and more TGF-beta (P = 0.06) than nonresponders and predicted Caucasian nonresponders with 83% sensitivity and 96% specificity. HCV genotype was not relevant to cytokine production (P = ns). Distribution of cytokine genetic polymorphisms (TNF-alpha, TNF-beta, IL-10, TGF-beta) was equivalent in all ethnic groups and did not predict clinical nonresponders. In summary, it appears that ethnicity may contribute to variable immune responses and therapeutic outcome. The cytokine profile among African Americans suggests a more robust immune response, which may complicate therapy with IFN. In contrast, the subnormal cytokine production among Caucasian responders may be more permissive to IFN therapy. Pretherapy cytokine production may allow prediction of drug resistance among Caucasians.
干扰素是丙型肝炎病毒（HCV）的主要治疗方法。然而，长期成功率较低，尤其是相对于白种人而言，非洲裔美国人的成功率更低，这可能是由于免疫能力的差异所致。本研究比较了25名健康的以及40名感染HCV的非洲裔美国人和白种人经PHA刺激的外周血中细胞因子的产生情况。根据治疗后的结果，将HCV患者分为干扰素应答者或无应答者。种族和基因型与干扰素应答相关。干扰素应答者100%为白种人，而无应答者中67%为白种人，33%为非洲裔美国人（P = 0.01）。100%的无应答者和50%的应答者存在基因型1（P < 0.05）。年龄、性别、肝脏组织学、谷丙转氨酶（ALT）和病毒滴度相当（无显著性差异）。健康个体的细胞因子产生情况显示出细胞因子水平的种族差异。与健康白种人相比，健康非洲裔美国人产生的白细胞介素-2（IL-2，P = 0.06）、肿瘤坏死因子-α（TNF-α，P = 0.06）更多，而产生的白细胞介素-10（IL-10，P = 0.05）更少。相比之下，干扰素-γ（IFN-γ）和转化生长因子-β（TGF-β）水平相当。HCV患者治疗前的细胞因子产生情况显示出类似的种族差异模式。非洲裔美国无应答者比白种人无应答者产生更多的IL-2（P = 0.06）和TNF-α（P = 0.02）。白种人和非洲裔美国无应答者的细胞因子水平与种族匹配的健康个体相当（P = 无显著性差异），而白种人应答者产生的IL-10（P < 0.05）和TGF-β（P < 0.05）水平低于正常。由于所有非洲裔美国人的干扰素治疗均失败，因此无法将细胞因子产生情况与治疗结果进行比较。然而，对白种人之间细胞因子产生情况的比较显示，应答者比无应答者产生的IL-10更少（P < 0.001），产生的TGF-β更多（P = 0.06），并且以83%的敏感性和96%的特异性预测白种人无应答者。HCV基因型与细胞因子产生无关（P = 无显著性差异）。细胞因子基因多态性（TNF-α、TNF-β、IL-10、TGF-β）在所有种族群体中的分布相当，并且不能预测临床无应答者。总之，种族似乎可能导致免疫反应和治疗结果的差异。非洲裔美国人的细胞因子谱表明其免疫反应更强，这可能使干扰素治疗复杂化。相比之下，白种人应答者中低于正常的细胞因子产生情况可能更有利于干扰素治疗。治疗前的细胞因子产生情况可能有助于预测白种人中的耐药性。
