Müller H, Takeshita M, Krause J, Schuster K, Kikuchi M, Stutte H J
Senckenbergisches Zentrum der Pathologie, J.W. Goethe-Universität, Frankfurt am Main.
Verh Dtsch Ges Pathol. 1992;76:164-8.
Primary biopsies from 149 patients with malignant lymphomas were examined by histological and immunohistochemical techniques. Twenty eight cases were classified as Hodgkin's disease and 121 as non-Hodgkin's lymphomas. The immunohistochemical distribution of cytokine expression (Il-1 alpha, Il-1 beta, Il-6 and TNF-alpha) was demonstrated in neoplastic cells and in tumor-associated macrophages (TAM). Neoplastic cells showed mostly weak positivity for TNF-alpha in 40% of Hodgkin's disease and in 20% of T cell lymphoma cases. Two groups of malignant lymphomas were established which differed in the numbers of cytokine expressing TAM. The first group consisted of malignant lymphomas which contained large quantities of cytokine-possessing TAM. In the second group significantly lower frequencies of cytokine expressing TAM were found. In both groups high and low grade malignant lymphomas were encountered. There was a significantly positive correlation between the number of Il-6 possessing TAM and the proliferation of lymphoma cells in only the non-Hodgkin's lymphomas. Our results suggest a paracrine tumor growth stimulating mechanism which is created by a self perpetuating cytokine production loop. A supposed cytokine produced by neoplastic cells dependent from their proliferative activity may induce Il-6 secretion by TAM. Il-6 in turn may stimulate the proliferation of the lymphoma cells without maturation thus leading to a self-sustaining growth.
采用组织学和免疫组化技术对149例恶性淋巴瘤患者的原发性活检标本进行了检查。28例被分类为霍奇金病，121例为非霍奇金淋巴瘤。在肿瘤细胞和肿瘤相关巨噬细胞（TAM）中显示了细胞因子表达（Il-1α、Il-1β、Il-6和TNF-α）的免疫组化分布。在40%的霍奇金病和20%的T细胞淋巴瘤病例中，肿瘤细胞对TNF-α大多呈弱阳性。建立了两组恶性淋巴瘤，它们在表达细胞因子的TAM数量上有所不同。第一组由含有大量具有细胞因子的TAM的恶性淋巴瘤组成。在第二组中，发现表达细胞因子的TAM频率明显较低。在两组中均发现了高分级和低分级恶性淋巴瘤。仅在非霍奇金淋巴瘤中，具有Il-6的TAM数量与淋巴瘤细胞增殖之间存在显著正相关。我们的结果提示了一种旁分泌肿瘤生长刺激机制，该机制由一个自我持续的细胞因子产生环形成。肿瘤细胞根据其增殖活性产生的一种假定细胞因子可能诱导TAM分泌Il-6。Il-6反过来可能刺激淋巴瘤细胞增殖而不发生成熟，从而导致自我维持生长。
