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

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 microg/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 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 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 In111-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.

Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia

“…Because the phenotypic characteristics agreed with the changes described for CMV-positive CVID patients, and the causal effect of IL-10 on thrombocytopenia was previously described31, we tested the possibility that the puzzling elevation of IL-10 in otherwise strongly activated phenotypes results from viral IL-10 homolog secretion. An ELISA assay specific for CMV IL-10 and EBV IL-10 showed no differences between CVID-AcT and other CVID samples.…”

“…The spleen is central to phagocytic clearance of opsonized platelets (as reviewed by Lo and Deane47). The platelet production was decreased in healthy volunteers receiving rhIL-1031, implying that the high levels of IL-10 found in CVID-AcT patients could impair the platelet production. Increased levels of IL-10 in CVID were described previously48.…”

Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population

“…Furthermore, decreased platelet production in humans in response to administration of recombinant IL-10 has also been documented. The same study postulated that IL-10-induced reduction in platelet count is possibly due to reduction in platelet production [50]. It is possible that similar mechanism of reduced platelet production due to high IL-10 levels is responsible for P. vivax -associated thrombocytopaenia in this study.…”

Differing Influences of Virus Burden and Immune Activation on Disease Severity in Secondary Dengue‐3 Virus Infections

“…The degree of thrombocytopenia was related to both virus burden and host factors affecting IL-10 or TNF-a (and sTNFR-II) production. Administration of recombinant IL-10 or TNF-a to human subjects has produced thrombocytopenia because of decreased platelet production (IL-10) [50] or increased platelet consumption (TNF-a) [51,52].…”