Selected Cytokines in Patients with Pancreatic Cancer: A Preliminary Report

Abstract

Background/AimsRecent experimental studies have suggested that various cytokines may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting.MethodsIn this study, we examined the levels of a broad panel of cytokines, including interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-23, as well as tumor necrosis factor alpha (TNFα) and granulocyte-colony stimulating factor (G-CSF) in patients with pancreatic adenocarcinoma (n = 43), other pancreatic malignancies (neuroendocrine [n = 10] and solid pseudopapillary tumors [n = 3]), and healthy individuals (n = 41).ResultsWe found that there were higher levels of IL-6, IL-8, IL-10 and TNFα in patients with pancreatic cancer compared to healthy controls (for all, at least p<0.03). Cancer patients had lower IL-23 concentrations than healthy individuals and patients diagnosed with other types of malignancies (for both, p = 0.002). Levels of IL-6, IL-8, IL-10, and IL-23 were significantly associated with the direct number of circulating bone marrow (BM)-derived mesenchymal or very small embryonic/epiblast-like stem cells (SCs) in patients with pancreatic cancer. Moreover, our study identified a potential ability of IL-6, IL-8, IL-10, IL-23, and TNFα levels to enable discrimination of pancreatic cancer from other pancreatic tumors and diseases, including acute and chronic pancreatitis and post-pancreatitis cysts (with sensitivity and specificity ranging between 70%–82%).ConclusionsOur study i) supports the significance of selected cytokines in the clinical presentation of pancreatic cancer, ii) highlights numerous associations between selected interleukins and intensified BMSCs trafficking in patients with pancreatic cancer, and iii) preliminarily characterizes the diagnostic potential of several cytokines as potential novel clinical markers of pancreatic cancer in humans.

Weight Loss, Diabetes, Fatigue, and Depression Preceding Pancreatic Cancer

“…IL-6 is linked to both pancreatic cancer 18-20 and to fatigue and depression 16,19,21 . Elevated levels of IL-6 have been found to be associated with clinical depression in patients with other cancers 15,22,23,24 .…”

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells

“…Similar results were also observed for another powerful mobilizer of BMSCs, granulocyte-colony stimulating factor (G-CSF), which is commonly used as a pharmaceutical agent to stimulate BMSC systemic mobilization in hematological settings. In multiple studies, researchers found that systemic G-CSF levels are also comparable between healthy individuals and patients with different types of pancreatic neoplasm [27,28]. This discrepancy may be explained by the presence of a high proinflammatory setting that accompanies pancreatic cancer development in humans.…”

“…This is associated with higher activity of proteolytic enzymes such as metalloproteinases, which are present both at the systemic and local levels [29,30] and may result in the inactivation of BMSC chemoattractants. Thus, researchers focused their efforts on other substances-mainly immune-related molecules, bioactive lipids, and growth factors-because these are involved in the formation of an immune-modulated microenvironment in pancreatic cancer, contribute to the development and/or progression of pancreatic malignancies, and, therefore, might potentially affect BMSC homeostasis and function [24,28,31]. Based on these studies, several substances that seemed to participate in a biochemical crosstalk between the BM and the developing pancreatic cancer have been identified.…”

“…Based on these studies, several substances that seemed to participate in a biochemical crosstalk between the BM and the developing pancreatic cancer have been identified. These involved anaphylatoxins of the complement cascade and/or biomolecules, such as C5a and C5b-9/membrane attack complex (MAC), sphingosine-and ceramide-derivatives, HGF, and cytokines (mainly interleukin [IL]-6 and IL-8) [24,28]. The exact function of these substances on the regulation of BMSC homeostasis has not been fully examined.…”

Chronic Pancreatitis as an Inductor of Pancreatic Cancer — Correlations With Inflammatory Pathways

“…Thereafter, many studies have pointed out that this cytokine has a role in autoimmune diseases, chronic inflammatory processes and, despite its name, in malignancy. Systemic levels of TNF-α together with various cytokines such as IL-6, Il-8, IL-10 were found to be significantly higher in patients with PDA compared to healthy subjects [23,24]. PDA cells are exposed to TNF-α secreted by the infiltrated macrophages but also to their own endogenous TNF-α.…”