Wetzler M, Estrov Z, Talpaz M, Markowitz A, Gutterman J U, Kurzrock R
Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston.
J Intern Med. 1993 Oct;234(4):417-20. doi: 10.1111/j.1365-2796.1993.tb00765.x.
Increasing evidence suggests that paraneoplastic syndromes may be mediated by tumour-related cytokine release, although the specific factor(s) involved remain poorly defined. Colony-stimulating factors (CSF) and interleukins (IL) promote colony growth in semi-solid media and, when administered in recombinant form, increase blood counts in patients. However, normal serum CSF levels in individuals with physiologic blood counts and the relationship between specific serum CSF levels and paraneoplastic leukaemoid reaction are not well established. In this study, we found that normal serum levels of granulocyte-macrophage CSF (GM-CSF), as measured by ELISA, were generally < 55 pg ml-1; IL-3, < 30 pg ml-1; and granulocyte CSF (G-CSF), < 50 pg ml-1. In contrast, high levels of GM-CSF (132 pg ml-1), but not G-CSF or IL-3, were found in a patient with a transitional cell carcinoma of the renal pelvis and increased leukocytosis correlating with the tumour burden. The GM-CSF was biologically active, as demonstrated by its ability to stimulate colony growth in vitro. Based on these results it appears that autonomous production of GM-CSF is one possible pathophysiologic mechanism underlying leukaemoid reaction in cancer patients.
越来越多的证据表明，副肿瘤综合征可能由肿瘤相关细胞因子的释放介导，尽管其中涉及的具体因子仍不清楚。集落刺激因子（CSF）和白细胞介素（IL）可促进半固体培养基中的集落生长，以重组形式给药时可增加患者的血细胞计数。然而，生理血细胞计数个体的正常血清CSF水平以及特定血清CSF水平与副肿瘤性类白血病反应之间的关系尚未明确。在本研究中，我们发现通过ELISA测定，粒细胞-巨噬细胞CSF（GM-CSF）的正常血清水平一般<55 pg/ml；IL-3<30 pg/ml；粒细胞CSF（G-CSF）<50 pg/ml。相比之下，在一名肾盂移行细胞癌患者中发现GM-CSF水平较高（132 pg/ml），而G-CSF或IL-3水平不高，且白细胞增多与肿瘤负荷相关。GM-CSF具有生物学活性，体外集落生长刺激能力证明了这一点。基于这些结果，GM-CSF的自主产生似乎是癌症患者类白血病反应的一种可能病理生理机制。
