A systematic review examining the relationship between cytokines and cachexia in incurable cancer

Abstract

Cancer cachexia is an unmet clinical need that affects more than 50% of patients with cancer. The systemic inflammatory response, which is mediated by a network of cytokines, has an established role in the genesis and maintenance of cancer as well as in cachexia; yet, the specific role of the cytokine milieu in cachexia requires elucidation. This systematic review aims to examine the relationship between cytokines and the cachexia syndrome in patients with incurable cancer. The databases MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, and Web of Science were searched for studies published between 01/01/2004 and 06/01/2020. Included studies measured cytokines and their relationship with cachexia and related symptoms/signs in adults with incurable cancer. After title screening (n = 5202), the abstracts (n = 1264) and the full-text studies (n = 322) were reviewed independently by two authors. The quality assessment of the selected papers was conducted using the modified Downs and Black checklist. Overall, 1277 patients with incurable cancer and 155 healthy controls were analysed in the 17 eligible studies. The mean age of the patients was 64 ± 15 (mean ± standard deviation). Only 34% of included participants were female. The included studies were assessed as moderate-quality to high-quality evidence (mean quality score: 7.8; range: 5-10). A total of 31 cytokines were examined in this review, of which interleukin-6 (IL-6, 14 studies) and tumour necrosis factor-α (TNF-α, 12 studies) were the most common. The definitions of cachexia and the weight-loss thresholds were highly variable across studies. Although the data could not be meta-analysed due to the high degree of methodological heterogeneity, the findings were discussed in a systematic manner. IL-6, TNF-α, and IL-8 were greater in cachectic patients compared with healthy individuals. Also, IL-6 levels were higher in cachectic participants as opposed to non-cachectic patients. Leptin, interferon-γ, IL-1β, IL-10, adiponectin, and ghrelin did not demonstrate any significant difference between groups when individuals with cancer cachexia were compared against non-cachectic patients or healthy participants. These findings suggest that a network of cytokines, commonly IL-6, TNF-α, and IL-8, are associated with the development of cachexia. Yet, this relationship is not proven to be causative and future studies should opt for longitudinal designs with consistent methodological approaches, as well as adequate techniques for analysing and reporting the results.

Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation

“…The terminal stage of malignant disease is frequently associated with cancer-related cachexia. It is explained as a systemic effect of pro-inflammatory factors such as IL-6, CXCL-8 and TNF-α in skeletal muscle, adipocytes and hepatocytes (Kasprzak 2021;Paval et al 2022). In many aspects, cancer-associated cachexia seems to be similar to that of a cytokine storm described in several viral infections (including COVID-19).…”

Hidden Agenda - The Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response in Inflammation-Induced Muscle Wasting

“…A physiological reduction in muscle mass (i.e., physiological muscle atrophy) mainly occurs due to unloading, such as in athletes with discontinued training, people with little physical activity, those having a sedentary life style or astronauts during space flight with a reduced gravitational load. Pathological muscle atrophy is caused by fasting, loss of innervation, due to neurological diseases (e.g., stroke, spinal cord or nerve injury), and accompanies various diseases, such as cancer ( 1 ), end-stage heart disease ( 2 ), end-stage renal disease ( 3 ), chronic obstructive pulmonary disease [COPD; ( 4 )] or sepsis ( 5 ). A reduction in muscle mass and function has severe consequences for affected patients and its prevention is of utmost importance to human health.…”

Research Progress of Liujunzi Decoction in the Treatment of Tumor-Associated Anorexia

“… 51 , 52 In addition, pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and interferon-γ (IFN-γ) may directly enter the central nervous system through the blood–brain barrier and bind to the corresponding receptors in the hypothalamus to promote the development of anorexia. 53 , 54 To appetite-promoting neurons NPY, in vitro hypothalamic cell experiment showed that 5-HT could interfere with the synthesis, transportation and secretion of NPY, which could enhance food intake, that is, the anorexia caused by 5-HT under the condition of cancer cachexia may be related to the NPY system. 48 On the other hand, there are other factors that do not directly affect appetite-regulated neurons that can cause CA.…”

“…Peripheral signals mainly involved in regulating appetite include leptin and ghrelin. 54 Leptin regulates appetite mainly by interacting with hypothalamic neuroendocrine pathways, inhibiting appetite regulation-related peptides such as NPY and orexin-A (OX-A) and stimulating hormones such as POMC. 58 Ghrelin can improve appetite, prevent weight loss, and promote the production of synthetic metabolic factors such as insulin and insulin-like growth factor 1 by stimulating growth hormone secretagogue receptor-1a (GHS-R1a) to promote the increase of synthetic metabolic hormones.…”