Suhadolnik R J, Reichenbach N L, Hitzges P, Sobol R W, Peterson D L, Henry B, Ablashi D V, Müller W E, Schröder H C, Carter W A
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Clin Infect Dis. 1994 Jan;18 Suppl 1:S96-104. doi: 10.1093/clinids/18.supplement_1.s96.
Levels of 2',5'-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase L were measured in extracts of peripheral blood mononuclear cells (PBMCs) from 15 individuals with chronic fatigue syndrome (CFS) before and during therapy with the biological response modifier poly(I).poly(C12U) and were compared with levels in healthy controls. Patients differed significantly from controls in having a lower mean basal level of latent 2-5A synthetase (P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from 10 persons with CFS had a mean basal level of activated 2-5A synthetase higher than the corresponding control value (P = .009). All seven pretherapy PBMC extracts tested were positive for the replication of human herpesvirus 6 (HHV-6). Therapy with poly(I).poly(C12U) resulted in a significant decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A synthetase/RNase L pathway in temporal association with clinical and neuropsychological improvement. The upregulated 2-5A pathway in CFS before therapy is consistent with an activated immune state and a role for persistent viral infection in the pathogenesis of CFS. The response to therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U) in this situation.
在15例慢性疲劳综合征（CFS）患者接受生物反应调节剂聚肌苷酸-聚胞苷酸（聚（I）·聚（C12U））治疗前后，测量其外周血单个核细胞（PBMC）提取物中2',5'-寡腺苷酸（2-5A）合成酶、生物活性2-5A和核糖核酸酶L（RNase L）的水平，并与健康对照者的水平进行比较。患者与对照者相比，潜在2-5A合成酶的平均基础水平较低（P <.0001）、生物活性2-5A的治疗前水平较高（P =.002）以及治疗前RNase L活性水平较高（P <.0001），差异均有统计学意义。10例CFS患者的PBMC提取物中活化2-5A合成酶的平均基础水平高于相应的对照值（P =.009）。所检测的所有7份治疗前PBMC提取物的人类疱疹病毒6型（HHV-6）复制均呈阳性。聚（I）·聚（C12U）治疗导致HHV-6活性显著降低（P <.01），并且2-5A合成酶/RNase L途径下调，与临床和神经心理学改善在时间上相关。治疗前CFS中上调的2-5A途径与激活的免疫状态以及持续性病毒感染在CFS发病机制中的作用一致。治疗反应表明在这种情况下聚（I）·聚（C12U）具有直接或间接的抗病毒活性。
