Various biomarkers, especially inflammatory markers like C-reactive protein (CRP), ferritin, fibrinogen, D-dimer and Interleukin 6 (IL-6) are associated with Covid-19 progression. And cytokine-mediated inflammation, also described as cytokine storm, plays an important role in severe cases of COVID-19 and is reported as a major cause of death.
IL-6 is produced by the stromal cells and is virtually present in all immune system cells in the lungs. Its secretion is stimulated by proinflammatory cytokines, especially interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα).
The implicated mechanism for COVID-19 cytokine-mediated inflammation relates to infection of the alveolar epithelial cells through the ACE2 receptor. The resulting acute inflammatory response activates macrophages as well as B and T lymphocytes that release pro-inflammatory cytokines directly promoting the ongoing inflammatory process. Under the stimulation of these inflammatory factors, a large number of inflammatory exudates and erythrocytes enter the alveoli, resulting in dyspnea, respiratory failure and death.
Baseline levels of human IL-6 in blood are known to be in the single pg/ml digits range and can increase up to thousands of pg/ml upon severe sepsis. Therefore, assays characterized by high sensitivity and a wide diagnostic window are needed for reliable determination of IL-6 in the bloodstream. See figure below.
Figure 1. Linearity of dilution using new IL-6 MAb pairs
Dilution linearity of IL-6 from septic patient’s plasma was measured in sandwich CLIA with MAb pair L152-L137. Plasma IL-6 concentration was measured with Roche Cobas 6000 analyser. The LoD of the MAb pair L152-L137 is 0.5 pg/mL
IL-6 is deemed to be superior to CRP and other markers of inflammation in predicting respiratory failure in Covid-19 [1,2]. It is further considered to be the most important driver of immune dysregulation and Acute Respiratory Distress Syndrome (ARDS) in Covid-19 [3,4,5,6].
We offer 7 new MAb pairs to IL-6 that are suitable for high sensitivity IL-6 assay development and a recombinant antigen suitable as a calibrator. The new antibodies have low cross-reactivity compared to other cognate interleukin human proteins, which results in high assay specificity. Our data sheets follow:
Cat. #2-IL6. Monoclonal anti-human Interleukin-6 (IL-6)
Cat. #8-hIL6. Recombinant human Interleukin-6 (IL-6).
References:
1. Adriaensen W., Matheï C., Vaes B., van Pottelbergh G., Wallemacq P., Degryse J.M. Interleukin-6 as a first-rated serum inflammatory marker to predict mortality and hospitalization in the oldest old: a regression and CART approach in the BELFRAIL study. Exp. Gerontol. 2015;69:53–61.
2. Baune B.T., Rothermundt M., Ladwig K.H., Meisinger C., Berger K. Systemic inflammation (Interleukin 6) predicts all-cause mortality in men: results from a 9-year follow-up of the MEMO Study. Age (Dordr) 2011;33(2) pp. 209–17.0.
3 Z. Qiao, W. Wang, L. Yin, et al. Using IL-6 concentrations in the first 24 h following trauma to predict immunological complications and mortality in trauma patients.
4. Wauquier N., Becquart P., Padilla C., Baize S., Leroy E.M. Human fatal zaire ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. PLoS Negl Trop Dis. 2010;4(10):e837.
5. Fredeking T.M., Zavala-Castro J.E., González-Martínez P. Dengue patients treated with Doxycycline showed lower mortality associated to a reduction in IL-6 and TNF levels. Recent Pat Antiinfect Drug Discov. 2015;10(1):51–58.
6. Tiwari N., Kapoor P., Dhole T.N. Antibody and inflammatory response-mediated severity of pandemic 2009 (pH1N1) influenza virus. J. Med. Virol. 2014;86(6):1034–1040.
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