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Changes in cytokine production during therapy with Granulocyte‐macrophage colony‐stimulating factor in patients with chronic hepatitis B
Author(s) -
Martín Julio,
Quiroga Juan A.,
Bosch Orencio,
Carreño Vicente
Publication year - 1994
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840200509
Subject(s) - granulocyte macrophage colony stimulating factor , medicine , cytokine , granulocyte macrophage colony stimulating factor receptor , immunology , chronic hepatitis , granulocyte , macrophage , macrophage colony stimulating factor , biology , virus , in vitro , biochemistry
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‐α, interleukin‐1β, interleukin‐6, interferon‐α and interferon‐γ were measured‐along with serum levels of soluble CD4, soluble CD8, soluble interleukin‐2 receptor and β2‐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‐α (p < 0.05) and interleukin‐1β (p < 0.02). Furthermore, spontaneous interleukin‐6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin‐1β 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 β2‐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 β2‐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. (Hepatology 1994;20:1156–1161).