Induction of IL-6 by Cytotoxic Chemotherapy Is Associated With Loss of Lean Body and Fat Mass in Tumor-free Female Mice

Elsea, Collin; Kneiss, Janet A.; Wood, Lisa J.

doi:10.1177/1099800414558087

Cited by 22 publications

(21 citation statements)

References 32 publications

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“…The chemotherapy drug cisplatin induces muscle atrophy by activating myostatin, IL-6, TNF-/, and IL-1b, which can be prevented by the orexigenic peptide ghrelin in the LLC-induced cachexia model [33]. Cyclophosphamide-, doxorubicin-, and 5-fluorouracil-induced cachexia is associated with increased circulating IL-6, followed by decreased insulin-like growth factor 1 (IGF-1) levels, and can be prevented by germline deletion of IL-6 [34]. Therefore, different chemotherapy agents induce cachexia via distinct mechanisms and further research is needed to understand their transduction pathways.…”

Section: Chemotherapy-induced Cachexiamentioning

confidence: 99%

Cytokine Signaling in Skeletal Muscle Wasting

Zhou

Liu

Liang

et al. 2016

Trends in Endocrinology & Metabolism

150

104

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Section: Chemotherapy-induced Cachexiamentioning

confidence: 99%

Cytokine Signaling in Skeletal Muscle Wasting

Zhou

Liu

Liang

et al. 2016

Trends in Endocrinology & Metabolism

150

104

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“…Previous study in tumour‐free model has documented a significant muscle loss during doxorubicin treatment, which is apparently unrelated to tumour growth. Given the fact that muscle loss in both humans and animals are closely associated with increased mortality in both cancer patient and elderly, development of other adjuvant intervention to preserve muscle mass, other than Q10 supplementation, should be regarded as a primary goal of cancer patients under doxorubicin therapy.…”

Section: Discussionmentioning

confidence: 96%

“…Doxorubicin has been used extensively for chemotherapy of cancer by the mechanism through which it systemically inhibits cell proliferation in vivo . One of the most devastating symptoms associated with mortality of cancer patients during the chemotherapy is development of sarcopenia . In humans, survival time in patients who were developed sarcopenia was significantly shorter than in patients who were not developed sarcopenia .…”

Section: Introductionmentioning

confidence: 99%

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Doxorubicin inhibits muscle inflammation after eccentric exercise

Huang

Saovieng

et al. 2016

J cachexia sarcopenia muscle

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BackgroundDoxorubicin, a widely used anti‐tumour drug, is known to cause muscle loss in cancer patients.MethodsFollowing an acute dose of doxorubicin injection (2.5 mg/kg per body weight), we examined macrophage distribution in rat soleus muscle challenged by eccentric exercise (downhill running). Long‐term doxorubicin treatment (one injection every 3 days) on muscle mass and survival were also determined.ResultsUnder non‐exercised condition, increased tumour necrosis factor (TNF)‐alpha mRNA and decreased IL‐10 mRNA were observed in soleus muscle of doxorubicin‐treated rats, compared with saline‐treated control rats. However, increases in inflammation score (leukocyte infiltration), nitrotyrosine level, and M1 macrophage (CD68+) invasion in exercised soleus muscle were absent in doxorubicin‐treated rats, whereas increased M2 macrophage (CD163+) localization in exercised muscle was less affected by doxorubicin. Despites coenzyme Q (Q10) supplementation significantly elevated TNF‐alpha mRNA, nitrotyrosine, and anti‐oxidant gamma‐glutamylcysteine synthetase (GCS) levels in non‐exercised soleus muscle, these pro‐inflammatory responses were also abolished in doxorubicin‐treated rats. Results from long‐term doxorubicin treatment show a significant muscle loss followed by an accelerated death, which cannot be reversed by Q10 supplementation.Conclusions(i) Doxorubicin impairs inflammation mechanism by depleting M1 macrophage in exercised skeletal muscle; (ii) Muscle loss and accelerated death during prolonged doxorubicin treatment cannot be reversed by Q10 supplementation.

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“…Findings from our recent study support this idea. Using a breast cancer chemotherapy treatment model we found that chemotherapy-induced weight loss was significantly greater in wild-type mice than in mice lacking IL-6, even after controlling for food intake and physical activity level (29). EBRT-related fatigue was associated with increased inflammatory gene expression in peripheral tissues and in the circulation.…”

Section: Discussionmentioning

confidence: 99%

Localized External Beam Radiation Therapy (EBRT) to the Pelvis Induces Systemic IL-1Beta and TNF-Alpha Production: Role of the TNF-Alpha Signaling in EBRT-Induced Fatigue

et al. 2016

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Prostate cancer patients undergoing localized external beam radiation therapy (EBRT) can experience a progressive increase in fatigue, which can affect physical functioning and quality of life. The purpose of this study was to develop a mouse EBRT prostate cancer treatment model with which to determine the role of pro-inflammatory cytokines in the genesis of EBRT-related fatigue. We assessed voluntary wheel-running activity (VWRA) as a proxy for fatigue, food intake and body weight in male C57BL/6 mice undergoing EBRT to the pelvis. In the first experiment, anesthetized male C57BL/6 mice underwent fractionated EBRT to the pelvis for a total dose of 68.2 Gy, thereby mimicking a clinically relevant therapeutic dose and frequency. The day after the last treatment, levels of IL-1β and TNF-α in plasma along with mRNA levels in liver, colon and whole brain were measured. EBRT-induced fatigue resulted in reduced body weight, diminished food intake, and increased plasma and tissue levels of IL-1β and TNF-α. In a follow-up experiment, we used TNF-α-deficient mice to further delineate the role of TNF-α signaling in EBRT-induced sickness behavior. EBRT-induced changes in fatigue, food intake and body weight were no different between TNF-α deficient mice and their wild-type counterparts. Taken together our data demonstrate that a clinically relevant localized irradiation of the pelvis induces a systemic IL-1β and TNF-α response and sickness behavior in mice, but the TNF-α signaling pathway alone does not independently mediate these effects.

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Induction of IL-6 by Cytotoxic Chemotherapy Is Associated With Loss of Lean Body and Fat Mass in Tumor-free Female Mice

Cited by 22 publications

References 32 publications

Cytokine Signaling in Skeletal Muscle Wasting

Cytokine Signaling in Skeletal Muscle Wasting

Doxorubicin inhibits muscle inflammation after eccentric exercise

Localized External Beam Radiation Therapy (EBRT) to the Pelvis Induces Systemic IL-1Beta and TNF-Alpha Production: Role of the TNF-Alpha Signaling in EBRT-Induced Fatigue

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