Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.
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.
Sosman
J A
JA
Section of Hematology/Oncology, University of Illinois at Chicago College of Medicine, 60612, USA. jasosman@tigger.cc.uic.edu
Verma
A
A
Moss
S
S
Sorokin
P
P
Blend
M
M
Bradlow
B
B
Chachlani
N
N
Cutler
D
D
Sabo
R
R
Nelson
M
M
Bruno
E
E
Gustin
D
D
Viana
M
M
Hoffman
R
R
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D002452:Cell Count; D004311:Double-Blind Method; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D008533:Megakaryocytes / Q000473:pathology; D010976:Platelet Count; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology*
D006454:Hemoglobins; D011994:Recombinant Proteins; D016753:Interleukin-10