In vivo effects of recombinant human interleukin-6 in primates: stimulated production of platelets.
In vivo effects of recombinant human interleukin-6 in primates: stimulated production of platelets.
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DOI：
10.1182/blood.v75.8.1602.1602
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发表时间：
1990-04
期刊：
影响因子：
20.3
通讯作者：
S. Asano;Akira Okano;K. Ozawa;T. Nakahata;T. Ishibashi;K. Koike;Hideo Kimura;Y. Tanioka;A. Shibuya;T. Hirano;T. Kishimoto;F. Takaku;Y. Akiyama
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文献类型：
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作者：
S. Asano;Akira Okano;K. Ozawa;T. Nakahata;T. Ishibashi;K. Koike;Hideo Kimura;Y. Tanioka;A. Shibuya;T. Hirano;T. Kishimoto;F. Takaku;Y. Akiyama
在食蟹猴中，以5至80 μ g/kg/d的剂量连续14天每天两次皮下注射重组人白细胞介素-6（rhIL-6）导致血小板计数呈剂量依赖性增加，通常在停止注射后持续超过1周。即使在5 μ g/kg/d剂量下，计数也达到注射前水平的约两倍或两倍以上，在超过20 μ g/kg/d剂量下，增加变为双相，停止注射后3天出现较高的第二个峰。以80 μ g/kg/d注射7天后的骨髓形态学分析显示，与对照组相比，巨核细胞的大小显著增加，表明促进了巨核细胞的成熟。rhIL-6治疗引起的其他变化包括剂量依赖性体重减轻、贫血、嗜中性粒细胞增多和单核细胞增多、血清C反应蛋白和α-1酸性糖蛋白水平升高以及血清白蛋白降低;所有这些变化均在停止注射后1周内恢复正常，并且在剂量低于10 μ g/kg/d时可耐受。这些结果表明，rhIL-6可能是治疗血小板减少症的有效策略。
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.