Cytokines in the pathogenesis of cancer cachexia

Argilés, Josep Μ.; Busquets, Sílvia; López‐Soriano, Francisco J.

doi:10.1097/01.mco.0000078983.18774.cc

Cited by 124 publications

(99 citation statements)

References 39 publications

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“…Both IL-6 and TNF-a levels were increased significantly in the TB group, which confirmed the role of TNF-a besides IL-6, in the pathogenesis of cancer cachexia in the C26 model. By contrast, levels of IL-4, in literature stated as an anti-cachectic cytokine (Argiles et al, 2003), showed a significant decrease in the TB group, which is in agreement with the cachectic state of the animals.…”

Section: Discussioncontrasting

confidence: 38%

“…In experiment B, the pro-inflammatory cytokines IL-6 and TNF-a were measured. These cytokines have been described as procachectic cytokines involved in different metabolic changes associated with wasting during cancer cachexia (Toomey et al, 1995;Argiles et al, 2003;Argiles, 2005). In literature, TNF-a levels measured in the C26 model were below the detection limit (Strassmann et al, 1992a;Soda et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

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Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia

et al. 2008

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The majority of patients with advanced cancer are recognised by impaired immune competence influenced by several factors, including the type and stage of the tumour and the presence of cachexia. Recently, a specific nutritional combination containing fish oil, specific oligosaccharide mixture, high protein content and leucine has been developed aimed to support the immune system of cancer patients in order to reduce the frequency and severity of (infectious) complications. In a recently modified animal model cachexia is induced by inoculation of C26 tumour cells in mice. In a pre-cachectic state, no effect was observed on contact hypersensitivity, a validated in vivo method to measure Th1-mediated immune function, after adding the individual nutritional ingredients to the diet of tumour-bearing mice. However, the complete mixture resulted in significantly improved Th1 immunity. Moreover, in a cachectic state, the complete mixture reduced plasma levels of pro-inflammatory cytokines and beneficially affected ex vivo immune function. Accordingly, the combination of the nutritional ingredients is required to obtain a synergistic effect, leading to a reduced inflammatory state and improved immune competence. From this, it can be concluded that the specific nutritional combination has potential as immune-supporting nutritional intervention to reduce the risk of (infectious) complications in cancer patients.

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Section: Discussioncontrasting

confidence: 38%

Section: Discussionmentioning

confidence: 99%

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia

et al. 2008

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“…In studies of rodents, injection of TNF-α and IL-1 initially reduces food intake. However, tolerance soon develops after repetitive administration of TNF-α [35]. The relation between plasma C3 and weight gain could hypothetically reflect the effects of these cytokines.…”

Section: Discussionmentioning

confidence: 99%

Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study

et al. 2005

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Aims/hypothesis: Mice that are deficient for complement factor 3 (C3) have shown resistance to weight gain, despite increased food intake. Cross-sectional studies of humans have reported correlations between C3 and obesity. This longitudinal study explored whether C3 predicts a large weight gain in middle-aged men. Methods: Plasma concentrations of C3 and complement factor 4 (C4) were measured in 2,706 non-diabetic healthy men aged between 38 and 50 years, who were re-examined after a mean period of 6.1 years. Results: After adjustments for initial weight, age, height and follow-up time, the odds of incurring large weight gain (75th percentile, ≥3.8 kg) were 1.00 (reference), 0.96 (95% CI:0.7-1.2), 1.1 (CI:0.9-1.5) and 1.4 (CI: 1.1-1.8), respectively, among men with C3 levels in the first, second, third and fourth quartiles (p for trend= 0.01) respectively. This relationship remained significant after further adjustments for lifestyle factors (physical inactivity, alcohol, smoking), metabolic factors (glucose or homeostasis model assessment values, cholesterol, triglycerides), inflammatory markers (fibrinogen, haptoglobin, ceruloplasmin, orosomucoid, α1-antitrypsin) and for C4. C4 was associated with weight gain after adjustments for initial weight, height, follow-up time and lifestyle factors, but not after adjustments for C3. Conclusions/interpretation: C3 is a risk factor for incurring large weight gain in middleaged men.

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“…[9,10] As a consequence of the acute-phase response, degradation of skeletal muscle proteins occurs, causing muscle atrophy. [16] The acute-phase response has been associated with hyper-metabolism and tissue catabolism, [21,22] and some acute-phase proteins such as C-reactive protein (CRP) have been shown to play a role in modulating the immune response and in predicting adverse outcomes in cancer patients. [5] CRP has been shown to be a strong marker of systemic inflammation in cancer patients and has been associated with the presence of anorexia, hyper-metabolism, accelerated weight loss, and shortened survival.…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

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Cytokines in the pathogenesis of cancer cachexia

Cited by 124 publications

References 39 publications

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia

Beneficial immune modulatory effects of a specific nutritional combination in a murine model for cancer cachexia

Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

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