COVID-19 Risk Stratification & Treatment Monitoring

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Randox Cytokine Testing Solutions

COVID-19 Risk Stratification and Treatment Monitoring

Simultaneous detection of up to 12 cytokines and growth factors from a single patient sample

Suitable for use with serum and plasma samples

Fully automated and semi-automated solutions available to suit all laboratory throughputs

Excellent analytical performance

Comprehensive test menu comprising 26 cytokines, cytokine receptors and growth factors

Availability of complementary quality controls for a complete testing package

Randox offer testing solutions for a comprehensive range of cytokines, cytokine receptors and growth factors designed to assist with COVID-19 risk stratification, monitoring of treatment efficacy and recovery. Utilising patented Biochip technology up to 12 cytokines and growth factors may be detected simultaneously from a single patient sample.

Cytokines play a vital role in the immune system and are known to be involved in the body’s response to a variety of inflammatory and infectious diseases. The over stimulation of these cytokines in response to infection is referred to as a ‘cytokine storm’ and strongly correlates with poor disease outcomes.

Cytokine storms are a common complication of SARS-CoV-2 (COVID-19) infection triggering viral sepsis, where viral replication and excessive, uncontrolled systemic inflammation may lead to pneumonitis, Acute Respiratory Distress Syndrome (ARDS), respiratory failure, shock, multiple organ failure, secondary bacterial pneumonia, and potentially death.

Cytokine Array I (12-plex)

Interleukin-1 (IL-1) is a regulatory and inflammatory cytokine, which exists in two forms, (IL-1α) and (IL-1β), which share 25% homology at amino acid level. IL-1α is produced as a biologically active 31 kDa precursor, which undergoes proteolytic cleavage yielding a 17 kDa protein of 159 amino acids.

There are two forms of IL-1, IL-1α and IL-1β ,which share 25% homology at amino acid level. IL-1β is synthesised as a biologically inactive precursor of 269 amino acids with a molecular mass of 31 kDa , which undergoes proteolytic cleavage by IL1 converting enzyme (ICE), which yields a 17kDa protein of 153 amino acids.

Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15 – 18 kDa protein which has varying degrees of glycosylation accounting for the observed molecular weight range. IL-2 regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity.

IL-4 is a glycoprotein synthesised as a precursor protein of 153 amino acids. The first 24 amino acid residue signal peptide is cleaved to produce a 129 amino acid 15-19 kDa protein.

IL-6 is synthesised as a precursor protein of 212 amino acids. The N-terminal 28 amino acid residue signal peptide is cleaved to produce a 21kDa protein. It has two potential N-glycosylation sites which have no effect on bioactivity. Different post-translational alterations such as glycosylation and phosphorylation give various forms of IL-6 with molecular masses of 21.5-28 kDa. The IL-6 receptor is a strongly glycosylated 80 kDa protein of 449 amino acids. Two different forms of the receptor have been described that bind IL-6 with differing affinities, a soluble form of the IL-6 receptor has also been described. The IL-6 receptor is expressed on T cells, mitogen activated B cells, peripheral monocytes and some macrophage and B cell derived tumour cell types. IL-6 also influences antigen-specific immune responses and inflammatory reactions.

IL-8 is a member of a structurally similar family of cytokines called chemokines, which demonstrate chemotactic activity for neutrophils. IL-8 is a non-glycosylated protein of 8 kDa and consists of 99 amino acids with a 22 residue signal peptide that is cleaved to generate a 77 amino acid sequence. IL-8 is produced in response to proinflammatory stimuli. It is produced by monocytes, macrophages, fibroblasts, endothelial cells, keratinocytes, melanocytes, hepatocytes, chondrocytes, T-cells, neutrophils, and astrocytes.

Interleukin-10 (IL-10), alternatively known as B-cell-derived T-cell growth factor (B-TCGF), cytokine synthesis inhibitory factor (CSIF) or T-cell growth inhibitory factor is a homodimeric protein with a molecular weight of 18 kDa. It is produced as a 178 amino acid residue precursor, which is cleaved to give a mature protein of 160 amino acids. IL-10’s primary function is as an anti-inflammatory agent, which inhibits cytokine production by T cells and natural killer cells caused by activation of monocytes/macrophages.

IFN-γ is a cytokine critical to both innate and adaptive immunity, and functions as the primary activator of macrophages, in addition to stimulating natural killer cells and neutrophils. Biologically active interferon gamma is a 20 or 25 kDa glycoprotein depending on its glycosylation state. This lymphokine is synthesised as a 166 amino acid sequence but is cleaved to give a 143 amino acid residue.

Human EGF is produced as a long precursor protein of 1207 amino acids which is released by proteolytic cleavage to give a globular protein of 6.4 kDa consisting of 53 amino acids. EGF is a common mitogenic factor that stimulates the proliferation of different types of cells, especially fibroblasts and epithelial cells. EGF activates the EGF receptor (EGFR/ErbB), which initiates, in turn, intracellular signaling.

Monocyte chemoattractant protein (MCP-1) is part of the chemotactic family of cytokines called chemokines. ). It is a 76 amino acid peptide and has a molecular weight of 8.6 kDa. MCP-1 in particular chondrocytes confirming its role in inflammatory responses. MCP-1 has been implicated in a wide variety of inflammatory diseases such as artherosclerosis, delayed hypersensitivity reactions, rheumatoid arthritis, alveotitis and idiopathic pulmonary fibrosis.

Tumour necrosis factor alpha (TNFα) is a 157 amino acid 26 kDa transmembrane protein which is secreted as a soluble mature 233 amino acid homotrimer of 17 kDa by proteolytic cleavage. TNF-α is secreted by macrophages in response to stimuli for the induction of systemic inflammation. The binding of the ligand TNF-α to the TNF receptor (TNFR1) initiates the pro-inflammatory and pro-apoptotic signaling cascades.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is secreted as a glycosylated homodimeric protein of 46 kDa that is made up of two 24 kDa subunits linked by disulphide bonds. VEGF is expressed by vascularised tissue such as pituitary, brain, lungs, kidneys, heart and adrenal glands, although it is assumed that all tissues have the potential to produce the growth factor. VEGF is stimulated when cells become deficient in oxygen or glucose or under inflammatory conditions.

Ordering Information

Cat. Number	Description	Kit Size
EV3508	Cytokine Array I Evidence	360 Biochips
EV3544	Cytokine Array I Evidence	180 Biochips
EV3513	Cytokine Array I Evidence Investigator	54 Biochips
EV3623	Cytokine Array I High Sensitivity Evidence Investigator	54 Biochips

Cytokine Array III (4-plex)

Interleukin-5 (IL-5) is a disulphide linked homodimer and belongs to a family of structurally related proteins that includes: interleukin-2, interleukin-4, macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor and growth hormone. It is a glycoprotein with the apparent molecular weight of recombinant IL-5 produced by mammalian cells in the range 45 to 60 kDa. The large variation in the molecular weight caused predominantly by the addition of heterogeneous carbohydrate chains.

Interleukin-15 (IL-15) is a 14 to 15 kDa protein of 114 amino acids. It contains 2 disulphide bonds and 2 N-linked glycosylation sites at the C-terminus1. IL-15 is expressed at the mRNA level in numerous normal human tissues in a broad range of cell types, including activated monocytes, dendritic cells, osteoclasts and fibroblasts. IL-15 has an essential role in natural killer (NK) cell development. It activates NK cell proliferation, cytotoxicity, and cytokine production and regulates NK cell/macrophage interaction. Studies have suggested that IL-15 may have a role in establishing innate immune responses and maintaining neutrophil-mediated inflammatory processes.

Granulocyte-macrophage colony stimulating factor (GMCSF) isolated from human sources is glycosylated with an apparent molecular mass of 23 kDa. The mature protein has 127 amino acids and is preceded by a hydrophobic leader sequence of 25 amino acids.

Macrophage inflammatory protein-1α (MIP-1α, CCL3) is a member of the CC chemokine subfamily whose members are known for chemotactic and proinflammatory effects and also for the promotion of homeostasis. MIP-1α is synthesised as a 92 amino acid precursor that is proteolytically processed to a mature protein of about 70 amino acids. MIP-1α has roles in inflammatory responses at sites of injury or infection by recruiting proinflammatory cells.

Ordering Information

Cat. Number	Description	Kit Size
EV3680	Cytokine Array III Evidence	180 Biochips
EV3678	Cytokine Array III Evidence Investigator	54 Biochips

Cytokine Array IV (5-plex)

Matrix metalloproteinase-9 (MMP-9) (gelatinase B) (92 kDa) is a member of the matrix metalloproteinase (MMP) family. MMP-9, one of the most widely investigated MMPs, regulates pathological remodeling processes that involve inflammation and fibrosis.

Soluble IL-2 receptor α (sIL-2Rα) results from the proteolytic cleavage of IL-2Rα at the cell surface by a membrane metalloproteinase; which is encoded by IL2RA on human chromosome. It’s widely noted in research that sIL-2Rα has been found in diseases caused by infections, autoimmune disease and organ transplantation.

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates pleiotropic roles in immune regulation, inflammation, hematopoiesis, and oncogenesis. The IL-6 receptor complex belongs to the haematopoietic receptor superfamily and mediates the biological activities of IL-6. It consists of two distinct membrane bound glycoproteins, an 80 kDa cognate receptor subunit (IL-6R) and a 130 kDa signal-transducing element (gp130). The gp130 subunit is expressed in almost all organs including heart, kidney, spleen, liver, lung, placenta and brain.

Tumour necrosis factor receptor I is one of two specific, high affinity cell surface receptors that function as transducing elements, providing the intracellular signal for cell responses to tumour necrosis factor (TNF). TNF is a proinflammatory cytokine mainly produced by stimulated monocytes, macrophages and T-lymphocyte subsets. It has a key role in host defence and immunosurveillance, mediating complex cellular responses of a different, even contrasting nature. TNFRI has a molecular mass of 55 kDa1 and is expressed by almost all cell types2 especially those cells that are susceptible to the cytotoxic action of TNFI. TNFRs are detectable in normal serum, but their concentration increases significantly in inflammatory and non-inflammatory diseases.

Tumour necrosis factor receptor II (TNFRII) is one of two specific, high affinity cell surface receptors that function as transducing elements, providing the intracellular signal for cell responses to tumour necrosis factor (TNF). TNF is a proinflammatory cytokine mainly produced by stimulated monocytes, macrophages and T-lymphocyte subsets. It has a key role in host defence and immunosurveillance, mediating complex cellular responses of a different, even contrasting nature. TNFRII has a molecular mass of 75 kDa1. Although TNFRII is expressed by almost all cell types, it is expressed primarily by cells of the immune system, cells of myeloid origin and endothelial cells.

Ordering Information

Cat. Number	Description	Kit Size
EV3659	Cytokine Array IV Evidence	180 Biochips
EV3661	Cytokine Array IV Evidence Investigator	54 Biochips

Cytokine Array V (5-plex)

Interleukin-3 (IL-3) possesses diverse biological activities and was discovered independently in studies on its biological activities. IL-3 is a heavily glycosylated protein with a polypeptide chain of 133 amino acids. It occurs naturally in a diversity of glycoforms generated by the addition of carbohydrate groups which results in size heterogeneity from 28 to 45 kDa. The function of the extensive carbohydrate modifications of the IL-3 polypeptide is not known however IL-3 has been linked with various diseases including colorectal and pancreatic cancers.

Interleukin-7 (IL-7) is classified as a type 1 short-chain cytokine of the haematopoietin family, a group that also includes IL-2, IL-3, IL-4, IL-5, GM-CSF, IL-9, IL-13, IL-15, M-CSF, and stem cell factor. The human gene for IL-7 is located on chromosome 8q12-13. The amino acid sequence of IL-7 predicts a molecular weight of 17.4 kDa, but glycosylation results in an active protein of 25 kDa. IL-7 appears to be involved in the development of an effective immune system and also in the generation and maintenance of strong and effective cellular immune responses directed against cancer cells, or infectious diseases.

Interleukin-12 (IL-12) is a 75 kDa heterodimeric glycoprotein cytokine composed of disulphide linked p40 (40 kDa) and p35 (35 kDa) subunits that are derived from separate genes1. p35 is expressed in a limiting and tightly regulated fashion by many different cell types, however the expression of p40, though in greater quantities than required for p70 formation, appears to be restricted to antigen presenting cells. IL-12 stimulates IFN production, which is essential in resistance to intracellular protozoan, fungal and bacterial infections and, in addition, tumours. Traditionally, IL-12 is accepted as an important mediator of autoimmunity and is involved in a number of autoimmune diseases including rheumatoid arthritis, psoriasis, inflammatory bowel disease and insulin-dependent diabetes mellitus.

Interleukin-13 (IL-13) is a 12 kDa protein that folds into four I-helical bundles. It contains four potential N-glycosylation sites and four cysteine residues that form two intramolecular disulphide bonds. IL-13 shares a number of structural features and functional characteristics with IL-4. The IL-13 protein is approximately 25% homologous1 with IL-4 and belongs to the same I-helix protein family. IL-13 plays a dominant role in resistance to most gastrointestinal nematodes and also modulates resistance to intracellular organisms by regulating cell mediated immunity. IL-13 is the central mediator of allergic asthma, where it regulates eosinophilic inflammation, mucus secretion, and airway hyperresponsiveness. Although IL-13 is associated primarily with the induction of airway disease, it also has anti-inflammatory properties.

Interleukin 23 (IL-23) is member of the IL-12 family. The IL-12 family consists of cytokines IL-12(p40p35), IL-23(p40p19) and IL-27(EBI13p28), and monomeric and homodimeric p401. IL-23 is a heterodimeric cytokine composed of disulphide linked p19 and p40 subunits. IL-23 plays a role in a signaling pathway that triggers inflammation.