IL-1 AND IL-6 RELEASE BY TUMOR-ASSOCIATED MACROPHAGES FROM HUMAN OVARIAN-CARCINOMA
IL-1 AND IL-6 RELEASE BY TUMOR-ASSOCIATED MACROPHAGES FROM HUMAN OVARIAN-CARCINOMA
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DOI：
10.1002/ijc.2910440508
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发表时间：
1989-11-15
影响因子：
6.4
通讯作者：
MANTOVANI, A
中科院分区：
文献类型：
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作者：
ERROI, A;SIRONI, M;MANTOVANI, A
本研究观察了18例卵巢癌腹水和7例卵巢癌实体瘤中肿瘤相关巨噬细胞（TAM）产生白细胞介素-Ⅰ（IL-Ⅰ）和IL-6的情况。这些是多效性单核因子，除了影响淋巴细胞的增殖和分化外，还作用于各种靶点，包括血管细胞和肝脏，因此可能参与某些恶性肿瘤表现的发病机制。在IL-6无活性的条件下，通过胸腺细胞共刺激物测定IL-1，并在8例病例中通过放射免疫测定法（RIA）测定IL-1。在7 TDI细胞系上测量IL-6作为杂交瘤生长因子（HGF）。TAM没有自发地释放明显水平的IL-1，并且在LPS刺激下，与血液单核细胞相比，TAM是这种单核因子的不良生产者。相比之下，TAM上清液含有高水平的HGF在故意刺激的情况下，暴露于LPS既不影响也不进一步增加这种单核因子的产生。TAM上清液的HGF活性被抗IL-6抗体完全阻断。8例卵巢癌患者的腹水中含有高水平的HGF活性，可被抗IL-6抗体阻断。因此，TAM在其释放功能相关的单核因子IL-1和IL-6的能力方面表现出解离。TAM产生的IL-6可能导致与恶性肿瘤相关的肝源性急性期蛋白升高。
Our study was designed to investigate the production of interleukin-I (IL-I) and IL-6 in tumor-associated macrophages (TAM) isolated from ascites (18 cases) or solid (7 cases) human ovarian carcinoma. These are pleiotropic monokines which, in addition to affecting proliferation and differentiation of lymphocytes, act on various targets, including vascular cells and liver, and may therefore be involved in the pathogenesis of certain manifestations of malignancy. IL-I was measured by the thymocyte co-stimulator assay, under conditions in which IL-6 was inactive, and, in 8 cases, by radioimmunoassay (RIA). IL-6 was measured as hybridoma growth factor (HGF) on the 7TDI cell line. TAM did not release appreciable levels of IL-I spontaneously and, upon LPS stimulation, were poor producers of this monokine compared to blood monocytes. In contrast, TAM supernatants contained a high level of HGF in the absence of deliberate stimulation, and exposure to LPS either did not affect or further augmented production of this monokine. HGF activity of TAM supernatants was completely blocked by anti-IL-6 antibodies. Ascites fluid from 8 ovarian-carcinoma patients contained high levels of HGF activity blocked by anti-IL-6 antibodies. Thus, TAM exhibit a dissociation in their capacity to release the functionally related monokines IL-I and IL-6. IL-6 produced by TAM may account for the elevation of liver-derived acute-phase proteins associated with malignancy.