Reference range and short- and long-term biological variation of interleukin (IL)-6, IL-17A and tissue necrosis factor-alpha using high sensitivity assays

Todd, John; Simpson, Peter; Estis, Joel; Torres, Victoria; Wub, Alan H.B.

doi:10.1016/j.cyto.2013.09.018

Cited by 66 publications

(57 citation statements)

References 37 publications

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“…In agreement with our hypothesis, mean IL‐6 levels were elevated with tendinopathy and dropped with treatment and an improvement of symptoms. With 1.9 ng/L postintervention, plasma IL‐6 concentration had returned to levels similar to those which had been established in a healthy reference population (1.89 ng/L) of 125 healthy subjects with a mean age of 49 years . However, our data emphasize that the IL‐6 response was not homogenous since IL‐6 levels were elevated in some but not all patients with Achilles tendinopathy.…”

Section: Discussionsupporting

confidence: 78%

Interleukin‐6 levels drop after a 12 week long physiotherapeutic intervention in patients with Achilles tendinopathy—a pilot study

2019

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For many years, tendinopathies were considered to be mainly degenerative. However, recent research indicates that chronic inflammation may be a feature of Achilles tendinopathy. Thus, the aim of this study was to investigate, if plasma levels of the inflammatory cytokine interleukin‐6 (IL‐6) are elevated in patients with chronic Achilles tendinopathy and if IL‐6 levels are affected by physiotherapeutic treatment, duration of symptoms or anatomical localization. Male patients with chronic insertional (n = 16) or mid‐portion (n = 15) Achilles tendinopathy were subjected to a physiotherapeutic intervention for 12 weeks. VISA‐A scores and blood plasma IL‐6 levels were determined before and after the intervention. From pre to post, VISA‐A scores (57 ± 13 to 74 ± 18 points) increased while mean plasma IL‐6 levels decreased significantly (2.5 ± 1.6 to 1.9 ± 0.7 ng/L). Patients with insertional did not significantly differ from patients with mid‐portion Achilles tendinopathy. Of all investigated parameters, pre‐ and post‐IL‐6 levels correlated weakly with age only (r = 0.388 and r = 0.389). In a subgroup of patients, inflammation appears to play a role in the context of Achilles tendinopathies, making IL‐6 a potential target for therapeutic interventions in this subgroup. Common factors leading to elevated IL‐6 levels need to be identified in future studies.

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Section: Discussionsupporting

confidence: 78%

Interleukin‐6 levels drop after a 12 week long physiotherapeutic intervention in patients with Achilles tendinopathy—a pilot study

2019

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“…To investigate biological significance of the inhibitors, we correlated inflammaging-associated markers among the two groups with and without inhibitors. IL-6 levels in both groups were significantly greater than a recently reported 95th percentile reference limit (4.45 pg/ml) in healthy adults younger than 65 years ( P < 0.001 for inhibiting and P < 0.01 for noninhibiting perons in one-sample t -tests versus 4.45 pg/ml) (Todd et al, 2013). Nonetheless, as shown in Table 1, IL-6 and CRP levels were not significantly different between individuals with ficolin-2 inhibitors and individuals without.…”

Section: Resultsmentioning

confidence: 64%

Ficolin-2 inhibitors are present in sera after prolonged storage at −80 °C

Geno

Kennedy

Sawyer

et al. 2016

PeerJ

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Ficolins can activate the lectin pathway of the complement system that provides innate immune protection against pathogens, marks host cellular debris for clearance, and promotes inflammation. Baseline inflammation increases with aging in a phenomenon known as “inflammaging.” Although IL-6 and C-reactive protein are known to increase with age, contributions of many complement factors, including ficolins, to inflammaging have been little studied. Ficolin-2 is abundant in human serum and can recognize many target structures; therefore, ficolin-2 has potential to contribute to inflammaging. We hypothesized that inflammaging would alter ficolin-2 levels among older adults and examined 360 archived sera collected from older individuals. We found that these sera had apparently reduced ficolin-2 levels and that 84.2% of archived sera exhibited ficolin-2 inhibitors, which suppressed apparent amounts of ficolin-2 detected by enzyme-linked immunosorbent assay. Fresh serum samples were obtained from donors whose archived sera showed inhibitors, but the fresh sera did not have ficolin-2 inhibitors. Ficolin-2 inhibitors were present in other long-stored sera from younger persons. Furthermore, noninhibiting samples and fresh sera from older adults had apparently normal amounts of ficolin-2. Thus, ficolin-2 inhibitors may arise as an artifact of long-term storage of serum at −80 °C.

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“…Baseline characteristics for the index cohort with measured IL‐6 are presented in Table . Mean age in the cohort was 69 ± 12 years, 1716 (74%) patients were male and median IL‐6 levels were 5.2 (2.8–10.2) pg/mL, with 1327 (56.9%) of patients having IL‐6 values greater than the previously reported 95th percentile of normal values (> 4.45 pg/mL) . Patients with higher levels of IL‐6 were older, more often had HF with preserved ejection fraction (HFpEF) and had a higher prevalence of anaemia, diabetes mellitus and AF.…”

Section: Resultsmentioning

confidence: 96%

“…Mean age in the cohort was 69 ± 12 years, 1716 (74%) patients were male and median IL-6 levels were 5.2 (2.8-10.2) pg/mL, with 1327 (56.9%) of patients having IL-6 values greater than the previously reported 95th percentile of normal values (> 4.45 pg/mL). 17 Patients with higher levels of IL-6 were older, more often had HF with preserved ejection fraction (HFpEF) and had a higher prevalence of anaemia, diabetes mellitus and AF. Additionally, patients with higher IL-6 levels were less likely to be able to perform the 6MWT and had an overall lower distance covered.…”

Section: Resultsmentioning

confidence: 99%

The clinical significance of interleukin‐6 in heart failure: results from the BIOSTAT‐CHF study

Markousis‐Mavrogenis

Tromp

Ouwerkerk

et al. 2019

European J of Heart Fail

206

148

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Aims Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)‐α were largely unsuccessful. Interleukin (IL)‐6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL‐6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. Methods and results Interleukin‐6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) ≤ 40%] of the BIOSTAT‐CHF cohort. The primary outcome was all‐cause mortality and HF hospitalization during 2 years, with all‐cause, cardiovascular (CV), and non‐CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL‐6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N‐terminal pro‐brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF‐α/IL‐1‐related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL‐6 levels. IL‐6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11–1.21), P < 0.001], all‐cause mortality [1.22 (1.16–1.29), P < 0.001] and CV as well as non‐CV mortality [1.16 (1.09–1.24), P < 0.001; 1.31 (1.18–1.45), P < 0.001], but did not improve discrimination in previously published risk models. Conclusions In a large, heterogeneous cohort of HF patients, elevated IL‐6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL‐6 as a potential therapeutic target in specific HF subpopulations.

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Reference range and short- and long-term biological variation of interleukin (IL)-6, IL-17A and tissue necrosis factor-alpha using high sensitivity assays

Cited by 66 publications

References 37 publications

Interleukin‐6 levels drop after a 12 week long physiotherapeutic intervention in patients with Achilles tendinopathy—a pilot study

Interleukin‐6 levels drop after a 12 week long physiotherapeutic intervention in patients with Achilles tendinopathy—a pilot study

Ficolin-2 inhibitors are present in sera after prolonged storage at −80 °C

The clinical significance of interleukin‐6 in heart failure: results from the BIOSTAT‐CHF study

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