Abstract
Background: 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.
Methods: 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.
Results: 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⩽0.03). Conversely, in coculture experiments performed with a neutralizing TNF antibody, a 50% reduction in tumor production of LIF and 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.
Conclusions: 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.
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Billingsley, K.G., Fraker, D.L., Strassmann, G. et al. Macrophage-derived tumor necrosis factor and tumor-derived of leukemia inhibitory factor and interleukin-6: Possible cellular mechanisms of cancer cachexia. Annals of Surgical Oncology 3, 29–35 (1996). https://doi.org/10.1007/BF02409048
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DOI: https://doi.org/10.1007/BF02409048