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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 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
StatePublished - Nov 23 2000

Keywords

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

ASJC Scopus subject areas

  • Hematology

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