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Review
. 2013 Mar;7(1):54-9.
doi: 10.1097/SPC.0b013e32835dabe3.

"V体育2025版" Inflammation and neural signaling: etiologic mechanisms of the cancer treatment-related symptom cluster

Lisa J Wood  1 , Kristianna Weymann
Affiliations
Review

Inflammation and neural signaling: etiologic mechanisms of the cancer treatment-related symptom cluster

Lisa J Wood et al. Curr Opin Support Palliat Care. 2013 Mar.

Abstract (VSports app下载)

Purpose of review: Cancer patients undergoing treatment with cytotoxic chemotherapeutic agents (CCAs) often experience a cluster of treatment-related symptoms, which include fatigue, loss of appetite, disturbed sleep, depressed mood, cognitive difficulties, and changes in body composition. This symptom cluster collectively referred to herein as cancer treatment-related symptoms (CTRSs) decrease quality of life, and physical and social functioning. The preclinical and clinical studies described in this review represent important progress in understanding potential underlying mechanisms of CTRS. VSports手机版.

Recent findings: Recent studies support a role for CCA-induced interleukin-1β (IL-1β) signaling in the cause of CTRS. CCAs may share a common ability to activate intracellular stress response pathways to trigger the synthesis, processing, and release of IL-1β from immune cells. Fatigue, sleep disturbance, and cognitive difficulties in cancer patients exposed to CCAs correlate with plasma levels of IL-6, IL-1 receptor antagonist, and soluble tumor necrosis factor receptor-I/II, surrogate markers of IL-1β-mediated central nervous system (CNS) inflammation. Additional preclinical work suggests IL-1β-mediated CNS inflammation may cause CTRS by altering hypothalamic and hippocampal functioning. V体育安卓版.

Summary: Although additional research is necessary to further establish the link between CCA exposure, IL-1β-mediated inflammatory processes and CTRS, these data provide hints for future studies and therapeutic approaches in ameliorating these symptoms in cancer patients V体育ios版. .

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures (VSports在线直播)

FIGURE 1
FIGURE 1
Proposed molecular mechanisms by which cytotoxic chemotherapeutic agents (CCAs) trigger the production of interleukin-1β (IL-1β) by macrophages. [1] The cytotoxic action of CCAs on tumor and healthy cells exposes tissue resident macrophages to several ‘danger signals’ including DNA, RNA, ATP, and bacterial products, and so on. These signals prime macrophages via activation of their surface Toll-like receptors (TLRs). Primed macrophages upregulate IL-1β gene expression via activation of the stress response proteins p38/JNK and nuclear factor-κB (NF-κB). The result is the accumulation of intracellular pro-IL-1β, the precursor to and biologically inactive form of IL-1β. [2] CCAs can also prime macrophages directly by activating ZAK, which prolongs and intensifies the activation of p38/JNK and synergizes with NF-κB to amplify the expression of pro-IL-1β. Nilotinib and sorafenib block ZAK and can consequently decrease CCA-mediated pro-IL-1β production. [3] CCA-induced formation of the NLRP3 inflammasome protein complex leads to cleavage of pro-IL-1β to mature IL-1β, which can then be released from the cell. [4] Release of mature IL-1β into the periphery stimulates the production of IL-1β and other inflammatory cytokines and chemokines, that is, tumor necrosis factor-α (TNF-α), IL-6, IL-1 receptor antagonist (IL-1RA), soluble tumor necrosis factor receptor-I/II (sTNFR-I/II), and so on. This IL-1β-driven systemic inflammatory response is the cause of sickness behavior, the symptoms of which are strikingly similar to cancer treatment-related symptoms.
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VSports app下载 - References

    1. Wang XS, Williams LA, Krishnan S, et al. Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. Brain Behav Immun. 2012;26:699–705. - PMC (V体育平台登录) - PubMed
    1. Oh HS, Seo WS. Systematic review and meta-analysis of the correlates of cancer-related fatigue. Worldviews Evid Based Nurs. 2011;8:191–201. - "VSports注册入口" PubMed
    1. Berger AM, Gerber LH, Mayer DK. Cancer-related fatigue: implications for breast cancer survivors. Cancer. 2012;118(8 Suppl):2261–2269. - PubMed

    1. Sauter KA, Wood LJ, Wong J, et al. Doxorubicin and daunorubicin induce processing and release of interleukin-1beta through activation of the NLRP3 inflammasome. Cancer Biol Ther. 2011;11:1008–1016 V体育平台登录. This article demonstrates for the first time that a CCA initiates the formation of the NLRP3 inflammasome to promote the secretion of IL-1β by immune cells. This finding supports the idea that symptoms related to exposure to cytotoxic agents may be caused by IL-1β.

    1. Wong J, Smith LB, Magun EA, et al. Small molecule kinase inhibitors block the ZAK-dependent inflammatory effects of doxorubicin. Cancer Biol Ther. 2012;14:56–63. This article demonstrates the central role that ZAK plays in doxorubicin-induced IL-1β production by immune cells. Nilotinib and sorafenib, which target ZAK, block doxorubicin-induced IL-1β production and consequently may be useful in reducing CTRSs VSports注册入口.

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