Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma.

Curtis J Henry,James Degregori,Theodore R Levin,Steven Haffner,Jennifer Salstrom,Andrii Rozhok,Rebecca L Sedjo,Tim Byers,Ralph D’Agostino,Dennis Ahnen

doi:10.1186/s12885-015-1115-2

Abstract

BackgroundInflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear.MethodsUsing the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin-10 (IL-10), IL-1β, IL-6, IL-17A, IL-2, IL-4, IL-7, IL-12(p70), interferon-γ (IFN-γ), macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1β (MIP-1β) were determined. Multiple logistic regression analyses were used to evaluate the association between adenoma prevalence and cytokine levels.ResultsThe presence of colorectal adenomas was not associated with significant increases in the systemic levels of proinflammatory (TNF-α, IL-6, IL-1β) or T-cell polarizing (IL-12, IL-2, IL-10, IL-4, IL-17, IFN-γ) cytokines. Furthermore, MCP-1 and RANTES levels were equivalent in the serum of study participants with and without adenomas.ConclusionsThese findings suggest colorectal adenoma prevalence may not be associated with significant alterations in systemic inflammation.

Highlights

Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state
Epidemiologic results Among the 194 Insulin Resistance Atherosclerosis Study (IRAS) Colon Study participants included in this analysis, older men who had previously reported being screened for colorectal cancer were significantly associated with adenoma prevalence in the bivariate analysis (Table 1)
No significant associations were observed between adenoma status and center, race/ethnicity, glucose tolerance status, body mass index (BMI), non-steroidal anti-inflammatory drugs (NSAIDs) use, and smoking status

Summary

Introduction

Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. Evidence pointing towards inflammation promoting disease progression from pre-malignant adenomatous polyps to advance staged CRC is suggested by the observation that plasma levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)-induced protein 10, and IL-8 increase in patients during each stage of disease progression [22]. The correlation between systemic cytokine levels and adenoma status was addressed in studies determining the role of anti-inflammatory dietary flavonols in colorectal adenoma incidence and prevention [24,25]. Another study assaying serum profiles between participants with colorectal adenomas, predisposing conditions such as IBD, and those with advanced-stage colon cancer observed that cytokine profiles could only accurately distinguish active IBD populations from those with CRC whereas the profiles between individuals with adenomas and CRC were not reliable enough to distinguish these two cohorts [7]

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