Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: Evidence for decreased platelet production

Jeffrey A. Sosman, Amit Verma, Steven Moss, Patricia Sorokin, Michael Blend, Basil Bradlow, Nasir Chachlani, David Cutler, Ronald Sabo, Mary Nelson, Edward Bruno, David Gustin, Marlos Viana, Ronald Hoffman

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26 Scopus citations

Abstract

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 x 109/l to 164 x 109/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 GMCSF appeared to be slightly increased in the serum. All subjects underwent Inn111-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.

Original languageEnglish (US)
Pages (from-to)104-111
Number of pages8
JournalBritish Journal of Haematology
Volume111
Issue number1
DOIs
Publication statusPublished - Nov 23 2000
Externally publishedYes

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Keywords

  • Anaemia
  • CFU-megakaryocyte
  • Interleukin 10
  • Platelets, thrombocytopenia

ASJC Scopus subject areas

  • Hematology

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