Billingsley K G, Fraker D L, Strassmann G, Loeser C, Fliot H M, Alexander H R
National Cancer Institute/National Institutes of Health, Bethesda, MD 20892, USA.
Ann Surg Oncol. 1996 Jan;3(1):29-35. doi: 10.1007/BF02409048.
The cellular basis for augmented cytokine production in the tumor-bearing host is not known. Recently leukemia inhibitory factor (LIF) and interleukin (IL)-6, produced by a variety of tumors, have been implicated as mediators of cachexia.
Five murine tumor cell lines were tested for the production of these cytokines. 4JK tumor was further tested to determine if IL-1, tumor necrosis factor (TNF), or cocultivation with RAW 264 cells augmented IL-6 or LIF production.
4JK from in vivo tumors produced significantly more IL-6 than did 4JK from culture, indicating that tumor production of IL-6 and LIF is potentially augmented by infiltrating macrophages. When 4JK was cocultured with RAW 264 cells, TNF, or IL-1 in vitro, a three- to 15-fold increase in tumor production of LIF and IL-6 was noted (p2 < or = 0.03). Conversely, in coculture experiments performed with a neutralizing TNF antibody, a 50% reduction in tumor production of LIF ad IL-6 was noted (p2 < 0.04). Resting RAW cells produced only minimal quantities of TNF; however, when RAW cells were exposed to tumor-conditioned supernatant from 4JK, their TNF production was markedly increased.
In the tumor microenvironment, host macrophages may be activated and produce inflammatory cytokines such as TNF. Local TNF then appears to act on tumor cells to stimulate production of IL-6 and LIF. Enhanced tumor production of cytokine mediators may contribute to deleterious effects of neoplastic growth on the host.
荷瘤宿主中细胞因子产生增加的细胞基础尚不清楚。最近，多种肿瘤产生的白血病抑制因子（LIF）和白细胞介素（IL）-6被认为是恶病质的介质。
检测了五种小鼠肿瘤细胞系中这些细胞因子的产生情况。对4JK肿瘤进一步检测，以确定IL-1、肿瘤坏死因子（TNF）或与RAW 264细胞共培养是否会增加IL-6或LIF的产生。
体内肿瘤来源的4JK产生的IL-6明显多于培养的4JK，这表明浸润的巨噬细胞可能会增强肿瘤IL-6和LIF的产生。当4JK在体外与RAW 264细胞、TNF或IL-1共培养时，LIF和IL-6的肿瘤产生量增加了3至15倍（P2≤0.03）。相反，在用中和性TNF抗体进行的共培养实验中，LIF和IL-6的肿瘤产生量减少了50%（P2<0.04）。静止的RAW细胞仅产生少量的TNF；然而，当RAW细胞暴露于4JK的肿瘤条件培养基上清液时，它们的TNF产生量明显增加。
在肿瘤微环境中，宿主巨噬细胞可能被激活并产生炎症细胞因子，如TNF。局部TNF似乎作用于肿瘤细胞以刺激IL-6和LIF的产生。肿瘤细胞因子介质产生的增强可能导致肿瘤生长对宿主产生有害影响。
