巨核细胞
血小板生成素
医学
血小板
安慰剂
内科学
细胞因子
白细胞介素11
免疫学
促炎细胞因子
骨髓
胃肠病学
白细胞介素
造血
炎症
生物
病理
干细胞
替代医学
遗传学
作者
Jeffrey A. Sosman,Amit Verma,Steven Moss,Patricia Sorokin,Michael J. Blend,Basil A. Bradlow,Nasir Chachlani,David L. Cutler,Ronald Sabo,Mary F. Nelson,Edward Bruno,David M. Gustin,Marlos Viana,Ronald Hoffman
标识
DOI:10.1111/j.1365-2141.2000.02314.x
摘要
Recombinant human interleukin 10 (rhuIL‐10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double‐blinded, placebo‐controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL‐10‐induced thrombocytopenia. Eight volunteers received 8 μg/kg/d of rhuIL‐10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 × 10 9 /l to 164 × 10 9 /l was observed in the IL‐10‐treated cohort ( P = 0·012). A fall in the haemoglobin mean levels was also observed in the IL‐10‐treated cohort from 13·7 to 11·7 g/dl ( P = 0·011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high‐powered field (HPF). A fall was observed in the number of megakaryocyte colony‐forming units (CFU‐MKs) after the administration of IL‐10 compared with those receiving the placebo ( P = 0·068). No difference in the change in granulocyte–macrophage CFUs (CFU‐GMs), mixed lineage CFUs (CFU‐GEMMs) or erythroid burst‐forming units (BFU‐Es) was observed when comparing the IL‐10‐ vs. placebo‐treated groups ( P > 0·465). Serum cytokine levels of thrombopoietin (TPO), IL‐6 and granulocyte–macrophage colony stimulating factor (GM‐CSF) were not decreased following IL‐10 administration. In fact, both TPO and GM‐CSF appeared to be slightly increased in the serum. All subjects underwent In 111 ‐labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets ( P = 0·012) was observed in the IL‐10‐treated group, but not in the placebo‐treated subjects.
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