Macrophage-Derived tumor necrosis factor and Tumor-Derived of leukemia inhibitory factor and interleukin-6: Possible cellular mechanisms of cancer cachexia

Kevin G. Billingsley, Douglas L. Fraker, Gideon Strassmann, Caroline Loeser, Helen M. Fliot, H. Richard Alexander

    Research output: Contribution to journalArticle

    22 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)29-35
    Number of pages7
    JournalAnnals of surgical oncology
    Volume3
    Issue number1
    DOIs
    StatePublished - Jan 1 1996

    Keywords

    • Cachexia
    • Cytokine
    • Interleukin-6
    • Leukemia inhibitory factor
    • Macrophage
    • Tumor necrosis factor

    ASJC Scopus subject areas

    • Surgery
    • Oncology

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