Biochip Array Profiling of Inflammatory Cytokines and Growth Factors In End-Stage Renal Disease: Hematological Implications?

Chronic inflammation is currently receiving a lot of attention because of its role in many disorders. Current studies suggest that chronic inflammation is a major risk factor in ESRD. Common comorbidities associated with ESRD include obesity, diabetes, cardiovascular disease, and the use of erythropoietin, each of which is also believed to be a chronic inflammatory state. Thus, ESRD is a multifaceted disease with many compounding factors which cause an elevation in inflammatory markers. The hematological implications include gross elevation of leukocyte cytokines, cellular proliferation disarray, and inflammatory up regulation. This study profiles several inflammatory and growth factors in the ESRD population.

Samples from ESRD patients on maintenance dialysis for at least 3 months over the age of 18 were included in this study. Additionally, control samples were obtained from healthy volunteers with no known kidney function. All markers were measured using the Randox Evidence Investigator (Antrim, United Kingdom), a novel biochip array technology which measures multiple markers simultaneously, depending on the array kit used. This study evaluated the cytokine and growth factor high-sensitivity array kit which measures IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, Vascular Endothelial Growth Factor (VEGF), Interferon-γ (INF-γ), Tumor Necrosis Factor-α (TNF-α), Monocyte Chemotactic Protein-1 (MCP-1), and Epidermal Growth Factor (EGF).

The table below includes levels of each marker tested in ESRD compared to controls given as percentage of the control. Of all the markers tested, IL-6 showed the greatest percentage increase in the ESRD samples at 430% of the controls. VEGF and INF-γ were both elevated at 260% of the controls. MCP-1, EGF, and TNF-α, were elevated at 200%, 140%, and 130% times controls respectively. IL-1α, IL-8, IL-10 were also elevated in the ESRD samples at 120%, 160%, and 140% times the controls, respectively. Interestingly, IL-1β levels were actually half or 50% times less in the ESRD samples compared to controls while IL-1 and IL-4 were just slightly reduced in the ESRD samples at 90% times the levels seen in controls.

Of the 12 markers measured, 9 were up regulated in the ESRD patients compared to controls. IL-1α, IL-6, IL-8, IL-10, VEGF, INF-γ, TNF-α, MCP-1, and EGF were all up regulated in the ESRD samples while IL-1β, IL-2, and IL-4 were down regulated in the ESRD samples. The up regulation of numerous inflammatory mediators and cellular factors convincingly demonstrates the severe inflammatory state of ESRD. The elevation of the interleukins, INF-γ, TNF-α, and MCP-1 displays an intense immunological activation of T-Cells, B-Cells, neutrophils, and macrophages. The increase in these cytokines also demonstrates the vascular and tissue damage occurring in this syndrome. VEGF and EGF are both elevated in the ESRD samples indicating a state of cellular proliferation, possibly in an attempt to replace damaged tissue caused by the heightened inflammatory state. In regards to the down regulation of IL-1β, both IL-1α and IL-1β bind to the same IL-1 receptor, it is possible that a portion of the IL-1β are bound to its receptor, falsely indicating low levels in the plasma samples. Potential role of erythropoietin treatment warrants additional investigations in the overall pathogenesis of ESRD.

No relevant conflicts of interest to declare.