TY - JOUR
T1 - Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers
T2 - Evidence for decreased platelet production
AU - Sosman, Jeffrey A.
AU - Verma, Amit
AU - Moss, Steven
AU - Sorokin, Patricia
AU - Blend, Michael
AU - Bradlow, Basil
AU - Chachlani, Nasir
AU - Cutler, David
AU - Sabo, Ronald
AU - Nelson, Mary
AU - Bruno, Edward
AU - Gustin, David
AU - Viana, Marlos
AU - Hoffman, Ronald
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Anaemia
KW - CFU-megakaryocyte
KW - Interleukin 10
KW - Platelets, thrombocytopenia
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UR - http://www.scopus.com/inward/citedby.url?scp=0033759187&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.2000.02314.x
DO - 10.1046/j.1365-2141.2000.02314.x
M3 - Article
C2 - 11091188
AN - SCOPUS:0033759187
SN - 0007-1048
VL - 111
SP - 104
EP - 111
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 1
ER -