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

Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proi nflammatory cytokines and has shown promise in the treatment of inflammator y bowel disease. Clinical trials have been accompanied by a reversible decl ine in platelet counts. We conducted a randomized, double-blinded, placebo- controlled, parallel group trial in 12 healthy Volunteers to investigate th e aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 mug/kg/d of rhuIL-10 subcutaneously, while four subjects received a plac ebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 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 th e IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant c hange was observed in the bone marrow cellularity or myeloid/ erythroid rat io 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 (C FU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (B FU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO), IL-6 and granuloc yte-macrophage colony stimulating factor (GM-CSF) were not decreased follow ing IL-10 administration, In fact, both TPO and GMCSF appeared to be slight ly increased in the serum. All subjects underwent In-111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration pr ior to and then on day 7 of treatment. A significant reduction in splenic s equestration of platelets (P = 0.012) was observed in the IL-10-treated gro up, but not in the placebo-treated subjects.