Are cytokines possible mediators of cancer cachexia?

Abstract

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.

Involvement of Interferon-γ in Microglial-Mediated Loss of Dopaminergic Neurons

“…It must be noted that cytokine detection in this assay may be hampered because of a lack in cytokine stability (Noguchi et al, 1996). In addition, it should also be stressed that cytokine blood levels do not necessarily reflect actions in the CNS.…”

Clodronate alleviates cachexia and prolongs survival in nude mice xenografted with an anaplastic thyroid carcinoma cell line

“…Various cytokines have been postulated to be responsible for the metabolic changes in cachexia of mouse xenograft models (Noguchi et al 1996). So far, only a few anti-cachectic drugs were applied to these animal models to evaluate their therapeutic efficacy (Tamura et al 1995, Kurebayashi et al 1999.…”

“…Proinflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, leukemia inhibitory factor (LIF), and interferon g, have been proposed as mediators of cancer cachexia (Noguchi et al 1996). Various agents demonstrated to suppress cytokine secretion, such as corticosteroid, megastrol acetate, medroxyprogesterone acetate, and thalidomide (Loprinzi et al 1993, Mantovani et al 1998, have been administered in attempts to retard or to halt progressive cachexia in cancer patients.…”

Changes in cytokine production and morphology of murine lymphoma NK/Ly cells in course of tumor development

“…IFN-γ could also be involved in cancer cachexia [32]. IFN-γ administration can increase survival outcomes in a variety of cancers [33] by stimulating cellular immunity [34].…”