Martín J, Quiroga J A, Bosch O, Carreño V
Hepatology Unit, Fundación Jiménez Díaz, Madrid, Spain.
Hepatology. 1994 Nov;20(5):1156-61.
Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.
重组人粒细胞巨噬细胞集落刺激因子疗法可显著降低血清乙肝病毒DNA水平，这与慢性乙肝患者培养的单核细胞中2',5'-寡腺苷酸合成酶活性增加有关。为评估慢性乙肝患者治疗期间的免疫功能变化，在9例慢性乙肝患者接受为期6周的粒细胞巨噬细胞集落刺激因子治疗前、治疗期间及治疗后，检测了肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、干扰素-α和干扰素-γ的自发及丝裂原诱导产生情况，同时检测了血清中可溶性CD4、可溶性CD8、可溶性白细胞介素-2受体和β2-微球蛋白水平。治疗在统计学上增强了肿瘤坏死因子-α（p < 0.05）和白细胞介素-1β（p < 0.02）的自发产生。此外，白细胞介素-6的自发产生与乙肝病毒DNA水平呈负相关（p < 0.03），白细胞介素-1β的自发产生与2',5'-寡腺苷酸合成酶活性呈正相关（p < 0.0005）。此外，治疗期间血清中可溶性白细胞介素-2受体（p < 0.01）、可溶性CD4（p < 0.01）和β2-微球蛋白（p < 0.05）水平在统计学上有显著升高。可溶性白细胞介素-2受体和可溶性CD4水平与乙肝病毒DNA水平呈负相关（p < 0.05），可溶性白细胞介素-2受体和β2-微球蛋白水平与2',5'-寡腺苷酸合成酶活性呈正相关（分别为p < 0.003和p < 0.02）。因此，给予重组人粒细胞巨噬细胞集落刺激因子可能通过改变免疫状态和增加细胞因子产生来降低乙肝病毒DNA水平。
