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重组人白细胞介素-3对造血祖细胞的体外和体内作用

[In vitro and in vivo effects of recombinant human interleukin-3 on hematopoietic progenitor cells].

作者信息

Seipelt G, Ottmann O G, Ganser A, Eder M, Lindemann A, Falk S, Stutte H J, Hübner K, Mertelsmann R, Hoelzer D

机构信息

Abteilung für Hämatologie, J. W. v. Goethe-Universität, Frankfurt.

出版信息

Verh Dtsch Ges Pathol. 1990;74:116-9.

PMID:1708567
Abstract

As part of a phase I/II clinical trial with recombinant human Interleukin-3 (rhIL-3), bone marrow and peripheral blood cells from patients treated with rhIL-3 were assessed in vitro for effects on the cycling status and frequencies of erythroid, myelomonocytic and multilineage progenitor cells. Treatment with rhIL-3 induced a pronounced increase in S-phase rate of BFU-E, CFU-GEMM and day 14 CFU-GM. Circulating CFU-GEMM and day 14 CFU-GM were increased on day 7 of therapy whereas circulating BFU-E were reduced in the majority of patients. After i.v. bolus injection of IL-3 an acute effect on the peripheral blood count with neutrophilia and, after an initial nadir, monocytosis was observed. IL-6 serum-levels increased in 5 out of 14 patients after IL-3 administration with concomitant side effects in 2 patients in whom IL-6 levels increased above 75 pg/ml. In the majority of the patients a stimulation of peripheral leukocytes and platelets was observed during the 15 day treatment course. In conclusion rhIL-3 induces a multilineage response in vivo by stimulating proliferation of hemopoietic progenitor cells with a resulting elevation in peripheral blood counts.

摘要

作为重组人白细胞介素-3(rhIL-3)I/II期临床试验的一部分,对接受rhIL-3治疗患者的骨髓和外周血细胞进行体外评估,以观察其对红系、骨髓单核系和多系祖细胞的细胞周期状态及频率的影响。rhIL-3治疗使BFU-E、CFU-GEMM和第14天CFU-GM的S期率显著增加。治疗第7天时,循环CFU-GEMM和第14天CFU-GM增加,而大多数患者的循环BFU-E减少。静脉推注IL-3后,外周血细胞计数出现急性变化,表现为中性粒细胞增多,在最初的最低点之后出现单核细胞增多。14例患者中有5例在给予IL-3后血清IL-6水平升高,其中2例患者出现伴随副作用,IL-6水平升高至75 pg/ml以上。在大多数患者中,在15天的治疗过程中观察到外周白细胞和血小板受到刺激。总之,rhIL-3通过刺激造血祖细胞增殖在体内诱导多系反应,导致外周血细胞计数升高。

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