Hematologic and immunologic evaluation of recombinant human interleukin-6 in patients with advanced malignant disease: evidence for monocyte activation.
Hematologic and immunologic evaluation of recombinant human interleukin-6 in patients with advanced malignant disease: evidence for monocyte activation.
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晚期恶性疾病患者重组人白细胞介素 6 的血液学和免疫学评估：单核细胞活化的证据。
DOI：
10.1097/00002371-199605000-00008
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Ritch,PS
中科院分区：
文献类型：
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作者：
Keever-Taylor,CA;Witt,PL;Truitt,RL;Ramanujam,S;Borden,EC;Ritch,PS
18例晚期癌症患者接受了4周的重组白细胞介素-6（rIL-6）皮下注射，剂量递增。对患者的血液学和免疫系统影响进行了评价。血液学监测包括WBC、分类计数、Hgb和Hct、血小板计数以及骨髓和外周血祖细胞评估。免疫学监测包括急性期反应物（APR）、免疫表型、血清细胞因子水平、精氨酸诱导蛋白和细胞因子信使RNA（mRNA）的评价。最大耐受剂量（MTD）为8.0 [μ] g/kg/天，神经皮质毒性是主要限制因素。所有患者均出现贫血，大多数患者出现发热和寒战。在整个治疗期间，APR增加。WBC在第2天一过性升高;粒细胞和单核细胞在第26天再次升高，而淋巴细胞降至基线或更低水平。血小板在第12天起反应，并在MTD下增加至第26天，对巨核细胞集落形成单位（CFU-Mk）无影响。外周血WBC和RBC祖细胞未受影响，但在骨髓中减少。T细胞百分比下降，对绝对数影响不大;观察到T细胞活化。CD 45 RO + T细胞减少，但对CD 8 + CD 28 + T细胞无明显影响。B细胞和自然杀伤（NK）细胞均未受到影响。然而，单核细胞效应的证据包括CD 71上调、精氨酸诱导蛋白2-5 A合成酶和新蝶呤诱导以及肿瘤坏死因子-α（TNF-α）mRNA增加。未检测到血清细胞因子，并且未诱导IL-1f [β]、IL-2和干扰素~（IFN~）的mRNA;然而，IL-4和IL-10的mRNA确实增加，表明Th 2样T细胞的活化。观察到1例混合肿瘤缓解。我们得出结论，IL-6单独对免疫系统以及造血系统具有全身活性，其在MTD时主要涉及APR的诱导、单核细胞的活化和扩增以及Th 2样T细胞的活化
Eighteen advanced cancer patients received weekday subcutaneous injections of recombinant interleukin-6 (rIL-6) for 4 weeks at escalating doses. Patients were evaluated for hematologic and immune system effects. Hematologic monitoring included WBC, differential, Hgb and Hct, platelet counts, and assessment of marrow and peripheral blood progenitors. Immunologic monitoring included evaluation of acute-phase reactants (APRs), immunophenotyping, serum cytokine levels, cytokine-induced proteins, and cytokine messenger RNA (mRNA). The maximal tolerated dose (MTD) was 8.0 [micro] g/kg/day, with neurocortical toxicity as the major limiting factor. All patients became anemic, and most had fever and chills. APRs were increased throughout treatment. WBCs increased transiently on day 2; granulocytes and monocytes increased again through day 26, whereas lymphocytes decreased to baseline or lower levels. Platelets responded by day 12 and increased through day 26 at the MTD with no effect on colony-forming unit-megakaryocyte (CFU-Mk). Peripheral WBC and RBC progenitors were not affected but decreased in the marrow. T-cell percentages declined with little effect on absolute numbers; T-cell activation was seen. CD45RO+ T cells decreased, but there was no significant effect on CD8+ CD28+ T cells. Neither B cells nor natural killer (NK) cells were affected. However, evidence of monocyte effects included upregulation of CD71, induction of the cytokine-induced proteins 2-5 A synthetase and neopterin, and increases in tumor necrosis factor-a (TNF-[alpha]) mRNA. Serum cytokines were undetected, and mRNA for IL-lf [beta], IL-2, and interferon~(IFN~) was not induced; however, mRNA for IL-4 and IL-10 did increase suggesting activation of Th2-like T cells. One mixed tumor response was seen. We conclude that IL-6 alone has systemic activity on the immune system, as well as the hematopoietic system, which at the MTD, primarily involves induction of APR, activation and expansion of monocytes, and activation of Th2-like T cells