In vivo effects of recombinant human interleukin-6 in primates: stimulated production of platelets.
In cynomolgus monkeys, twice daily subcutaneous injections of recombinant human interleukin-6 (rhIL-6) at doses of 5 to 80 micrograms/kg/d for 14 consecutive days caused dose-dependent increases in platelet count, usually continuing for more than 1 week after cessation of the injections. The count reached a level approximately twofold or more above the preinjection level even at 5 micrograms/kg/d, and at doses of more than 20 micrograms/kg/d, the increase became biphasic with a higher second peak 3 days after cessation of the injections. Morphologic analysis of the bone marrow after the 7 day-injections with 80 micrograms/kg/d revealed a marked increment in size of megakaryocytes compared with control, indicating the promotion of megakaryocyte maturation. Other changes attributable to the rhIL-6 treatment include dose-dependent loss of body weight, anemia, neutrophilia and monocytosis, elevation of serum C-reactive protein and alpha-1 acid glycoprotein levels, and decrease of serum albumin; all of which returned to normal within 1 week after cessation of the injections and were tolerable at doses of less than 10 micrograms/kg/d. These findings suggest that rhIL-6 may be an effective strategy for the treatment of thrombocytopenia.
Asano
S
S
Department of Hematology/Oncology, University of Tokyo, Japan.
Okano
A
A
Ozawa
K
K
Nakahata
T
T
Ishibashi
T
T
Koike
K
K
Kimura
H
H
Tanioka
Y
Y
Shibuya
A
A
Hirano
T
T
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007267:Injections; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D008251:Macaca / Q000097:blood*; D008252:Macaca fascicularis / Q000097:blood*; D008533:Megakaryocytes / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000502:physiology
D015850:Interleukin-6; D011994:Recombinant Proteins