Interleukin-1?? system in anorectic catabolic tumor-bearing rats

Turrin, Nicolas P.; Ilyin, Sergey E.; Gayle, Dave; Plata‐Salamán, Carlos R.; Ramos, Eduardo J.B.; Laviano, Alessandro; Das, Undurti N.; Inui, Akio; Meguid, Michael M.

doi:10.1097/01.mco.0000134373.16557.92

Cited by 44 publications

(28 citation statements)

References 37 publications

(43 reference statements)

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“…Elevations in proinflammatory cytokines (IL-1␤, IL-6, and TNF-␣) have been associated with experimental and clinical anorexia (26,35,43,60) and with increased resting energy expenditure in patients with end-stage renal disease and human immunodeficiency virus infection (27,50). Ghrelin has been used with success to treat both animals and humans with conditions that are associated with elevated cytokine levels, such as cancer cachexia (9,22,42), cardiac cachexia (14, 38 -41), lipopolysaccharide injection (63), sepsis (69), renal failure (55), and chronic kidney disease (8).…”

Section: Discussionmentioning

confidence: 99%

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Peripheral ghrelin treatment stabilizes body weights of senescent male Brown Norway rats at baseline and after surgery

Yukawa¹,

Weigle²,

Davis³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Section: Discussionmentioning

confidence: 99%

“…Elevated levels of proinflammatory cytokines are associated with anorexia in humans and animals (26,27,35,43,50,60). Ghrelin has been shown to decrease both proinflammatory cytokine levels in the plasma of an arthritic rat model as well as the chronic kidney failure model, and in proinflammatory cytokine production by cultured human cells (8,12,28,63).…”

mentioning

confidence: 99%

Peripheral ghrelin treatment stabilizes body weights of senescent male Brown Norway rats at baseline and after surgery

Yukawa¹,

Weigle²,

Davis³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In patients with OGC, a number of primary and secondary causes of reduced dietary intake are at work simultaneously, including dysphagia (McKernan et al, 2008), early satiety (Davis et al, 2006), chronic nausea (McKernan et al, 2008), alterations in circulating neuroendocrine hormones (e.g., ghrelin (Isomoto et al, 2005) and leptin (Huang et al, 2005;Zhao et al, 2007)), hypogeusia/hyposmia (Plata-Salaman, 2000), and cytokine-induced central anorexia (Plata-Salaman, 2001;Turrin et al, 2004). Assuming that MIC-1 may be a modulator of appetite in humans, the complex constellation of additional factors also controlling food intake may explain why plasma MIC-1 concentrations did not correlate with nutritional status in this study.…”

Section: Crp (Mg Lmentioning

confidence: 99%

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

et al. 2010

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BACKGROUND: Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). METHODS: Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of X10 mg l -1 or modified Glasgow prognostic score (mGPS) of X1), and nutritional status were assessed in newly diagnosed OGC patients (n ¼ 293). Healthy volunteers (n ¼ 35) served as controls. RESULTS: MIC-1 was elevated in patients (median ¼ 1371 pg ml -1 ; range 141 -39 053) when compared with controls (median ¼ 377 pg ml -1 ; range 141 -3786; Po0.001). Patients with gastric tumours (median ¼ 1592 pg ml -1 ; range 141 -12 643) showed higher MIC-1 concentrations than patients with junctional (median ¼ 1337 pg ml -1 ; range 383 -39 053) and oesophageal tumours (median ¼ 1180 pg ml -1 ; range 258 -31 184; P ¼ 0.015). Patients showed a median weight loss of 6.4% (range 0.0 -33.4%), and 42% of patients had an mGPS of X1 or plasma CRP of X10 mg l -1 (median ¼ 9 mg l -1 ; range 1 -200). MIC-1 correlated positively with disease stage (r 2 ¼ 0.217; Po0.001), age (r 2 ¼ 0.332; Po0.001), CRP (r 2 ¼ 0.314; Po0.001), and mGPS (r 2 ¼ 0.336; Po0.001), and negatively with Karnofsky Performance Score (r 2 ¼ À0.269; Po0.001). However, although MIC-1 correlated weakly with dietary intake (r 2 ¼ 0.157; P ¼ 0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median ¼ 204 days; 95% CI 157 -251) when compared with patients with MIC-1 levels in the lower three quartiles (median ¼ 316 days; 95% CI 259 -373; P ¼ 0.036), but MIC-1 was not an independent prognostic indicator. CONCLUSIONS: There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC.

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“…IL-1b and leptin (98) decrease the expression of ghrelin mRNA in the stomach, whereas IL-6 produced in various cells, including adipocytes, regulates leptin production (99). These findings suggest that cytokines have an important role in energy balance through the persistent activation of the leptin system and the inhibition of the ghrelin-NPY/agouti-related peptide orexigenic network in tumor-bearing rats (87).…”

Section: Rikkunshito As An Activator Of Ghrelin Signalingmentioning

confidence: 60%

Cancer Cachexia Pathophysiology and Translational Aspect of Herbal Medicine

Suzuki¹,

Asakawa²,

Amitani³

et al. 2013

Japanese Journal of Clinical Oncology

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About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. In particular, tumor necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a depression in protein synthesis, an increase in protein degradation or a combination of both. Cancer patients suffer from the reduction in physical function, tolerance to anti-cancer therapy and survival, while many effective chemotherapeutic agents for cancer are burdened by toxicities that can reduce patient's quality of life or hinder their effective use. Herbal medicines have been widely used to help improve such conditions. Recent studies have shown that herbal medicines such as rikkunshito enhance ghrelin signaling and consequently improve nausea, appetite loss and cachexia associated with cancer or cancer chemotherapy, which worsens the quality of life and life expectancy of the patients. The multicomponent herbal medicines capable of targeting multiple sites could be useful for future drug discovery. Mechanistic studies and identification of active compounds could lead to new discoveries in biological and biomedical sciences.

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Interleukin-1?? system in anorectic catabolic tumor-bearing rats

Abstract: This suggests that IL-1beta and its receptor may play a significant role in this model of cancer-associated anorexia. In vivo, the characterization of cytokine components in the brain may provide data for potential pharmacological interventions to ameliorate the anorexia of disease.

Cited by 44 publications

References 37 publications

Peripheral ghrelin treatment stabilizes body weights of senescent male Brown Norway rats at baseline and after surgery

Peripheral ghrelin treatment stabilizes body weights of senescent male Brown Norway rats at baseline and after surgery

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

Cancer Cachexia Pathophysiology and Translational Aspect of Herbal Medicine

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