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Home > Coronavirus > Cytokine Release Syndrome

Cytokine Release Syndrome

Cytokines are small proteins produced in the body to mediate cell signaling and regulation of the immune system. Cytokine Release Syndrome is characterized by an immune over-response, where the majority of the damage done to the host is due to an attack by the immune system rather than a direct cytotoxic effect by the pathogen. This systemic inflammatory response is mediated by the release (by immune cells) of inflammatory cytokines such as IFN-alpha, IFN-gamma, IL-1, IL-1 beta, IL-2, IL-2R, IL-6, IL-8, IL-10, IL-12, IL-17D, IL-18, IL-33, TNF-alpha, TGF-beta, and chemokines such as CCL2, CCL3, CCL5, CXCL8, CXCL9, and CXCL10. The overproduction of inflammatory cytokines leads to an attack on multiple organ systems resulting in ARDS, multi-organ failure, and hypotensive shock (Li, X., 2020; Huang, C., 2020). Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause a severe and highly lethal respiratory disease in humans. These diseases are also characterized by a prominent pro-inflammatory response and mediated by release of cytokines (Chan, J.F., 2015).

Cytokine Release Syndrome

Cytokine Release Syndrome Targets

Interleukin-1 Alpha (IL-1A)

IL-1A is a pro-inflammatory cytokine and an important mediator of local and systemic inflammation. Excessive IL-1A release during viral infections can cause lung and tissue inflammation, fever, and fibrosis. IL-1A suppression has been found to be effective in many inflammatory diseases, including rheumatoid arthritis.

All IL-1A Products

Interleukin-1 Beta (IL-1B)

IL-1B is a potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, it induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. It promotes differentiation of the TH17 subset of T-cells.

All IL-1B Products

Interleukin-2 (IL-2)

Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and many other activities crucial to regulation of the immune response. It can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.

All IL-2 Products

Interleukin-2 Receptor (IL-2R)

The increased expression of IL-2R and IL-6 in serum is expected to predict increased severity of COVID-19 pneumonia and a poorer patient prognosis (Chen, L., 2020).

All IL-2R Products

Interleukin-2 Receptor Gamma (IL-2RG)

IL-2RG is a common subunit for the receptors for a variety of interleukins. Probably in association with IL-15RA, it is involved in the stimulation of neutrophil phagocytosis by IL-15.

All IL-2RG Products

Interleukin-6 (IL-6)

IL-6 is a cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response, plays an essential role in the final differentiation of B-cells into immunoglobulin-secreting cells, and is involved in lymphocyte and monocyte differentiation. IL-6 acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells, and cells of the central nervous system (CNS). It is also required for the generation of TH17 cells.

Increased expression of IL-2R, D-Dimer, and IL-6 in serum was associated with increased severity of 2019-nCoV pneumonia and poorer patient prognosis (Russell, B., 2020) (Chen, L., 2020).

All IL-6 Products

Interleukin-8 (IL-8)

IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. IL-8 is released from several cell types in response to an inflammatory stimulus.

All IL-8 Products

Interleukin-10 (IL-10)

IL-10 inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF, and GM-CSF. IL-10 is produced by activated macrophages and by helper T-cells.

All IL-10 Products

Interleukin-17D (IL-17D)

IL-17D induces expression of IL-6, CXCL8/IL-8, and CSF2/GM-CSF from endothelial cells.

All IL-17D Products

Interleukin-17A (IL-17A)

IL-17A is part of the ligand for IL-17RA and IL-17RC. The heterodimer formed by IL-17A and IL-17F is the ligand for the heterodimeric complex formed by IL-17RA and IL-17RC. It is involved in inducing stromal cells to produce proinflammatory and hematopoietic cytokines.

All IL-17A Products

Interleukin-18 (IL-18)

IL-18 augments natural killer cell activity in spleen cells and stimulates interferon gamma production in T-helper type I (TH1) cells. IL-18 belongs to the IL-1 family.

All IL-18 Products

Interferon Gamma Receptor 1 (IFNGR1)

IFNGR1 associates with IFNGR2 to form the receptor for interferon gamma (IFNG). Ligand binding stimulates activation of the JAK/STAT signaling pathway.

All IFNGR1 Products

Tyrosine-Protein Kinase JAK2

JAK2 is a non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation, and histone modification. The JAK2 pathway mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, JAK2 plays a pivotal role in signal transduction via its association with type I receptors, such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), and thrombopoietin (TPOR); or with type II receptors, including IFN-alpha, IFN-beta, IFN-gamma, and multiple interleukins. JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation, which may lead to the hypertension observed in some COVID-19 patients (Guilluy C, 2010).

All JAK2 Products

NACHT, LRR and PYD domains-containing protein 3(NLRP3)

As the sensor component of the NLRP3 inflammasome, NLRP3 plays a crucial role in innate immunity and inflammation. The SARS-CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-mediated ubiquitination of apoptosis-associated speck-like protein, containing a caspase recruitment domain (ASC). Since the ORF3a domain in SARS-CoV-2 is approximately 73% similar to SARS-CoV, it is likely to be involved in a similar mechanism (Siu, K.L., 2019).

All NLRP3 Products

Tumor Necrosis Factor-alpha (TNFa)

The TNF family of receptors and cytokines is very large and this family is frequently targeted by drugs. TNFa is a pro-inflammatory cytokine involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa, and refractory asthma. TNFa inhibitors act by suppressing the physiologic response to TNFa. Inhibition of TNFa can be achieved with a monoclonal antibody, such as infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi), or with a receptor fusion protein, etanercept (Enbrel). Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19 (Russell B., 2020).

All TNFa Products

C-C motif chemokine 2 (MCP1/CCL2)

C-C motif chemokine 2 (MCP1/CCL2) is a chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. CCL2 augments monocyte anti-tumor activity, and has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates like psoriasis, rheumatoid arthritis, and atherosclerosis.

All MCP1/CCL2 Products

Granulocyte Colony-Stimulating Factor (MIP1A/GCSF)

Granulocyte/macrophage colony-stimulating factors are cytokines that act during hematopoiesis by controlling the production, differentiation, and function of granulocytes, monocytes, and macrophages. GCSF induces granulocytes and belongs to the IL-6 superfamily.

All MIP1A/GCSF Products

References
  • Chan, J. F., Lau, S. K., To, K. K., Cheng, V. C., Woo, P. C., & Yuen, K. Y. (2015). Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease. Clinical Microbiology Reviews, 28(2), 465–522.
  • Chen, L., Liu, H. G., Liu, W., Liu, J., Liu, K., Shang, J., Deng, Y., & Wei, S. (2020). Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese Journal of Tuberculosis and Respiratory Diseases, 43(0), E005. Advance online publication.
  • Guilluy, C., Brégeon, J., Toumaniantz, G., Rolli-Derkinderen, M., Retailleau, K., Loufrani, L., Henrion, D., Scalbert, E., Bril, A., Torres, R. M., Offermanns, S., Pacaud, P., & Loirand, G. (2010). The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nature Medicine, 16(2), 183–190
  • Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England), 395(10223), 497–506.
  • Russell, B., Moss, C., George, G., Santaolalla, A., Cope, A., Papa, S., & Van Hemelrijck, M. (2020). Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience, 14, 1022.
  • Siu, K. L., Yuen, K. S., Castaño-Rodriguez, C., Ye, Z. W., Yeung, M. L., Fung, S. Y., Yuan, S., Chan, C. P., Yuen, K. Y., Enjuanes, L., & Jin, D. Y. (2019). Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. FASEB journal: Official Publication of the Federation of American Societies for Experimental Biology, 33(8), 8865–8877.

All Cytokine Release Syndrome Products

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JAK2 Antibody - Anti-IKB Alpha antibody IHC of human skeletal muscle. Immunohistochemistry of formalin-fixed, paraffin-embedded tissue after heat-induced antigen retrieval. Antibody concentration 20 ug/ml.
Select
JAK2 Rabbit anti-Human Polyclonal (Tyr221) Antibody
IHC, IHC-P
Unconjugated
50 µg/$485
JAK2 Antibody - JAK2 antibody flow cytometric analysis of paraformaldehyde fixed K562 cells (blue line), permeabilized with 0.5% Triton. Primary incubation 1hr (10ug/ml) followed by Alexa Fluor 488 secondary antibody (0.4ug/ml). IgG control: Unimmunized goat IgG (black line) followed by Alexa Fluor 488 secondary antibody.
Select
JAK2 Goat anti-Human Polyclonal Antibody
ELISA, Peptide-ELISA
Unconjugated
100 µg/$405
IL-1B / IL-1 Beta Antibody - Immunohistochemistry of Human IL1 beta antibody. Tissue: medullary lymph node. Fixation: formalin fixed paraffin embedded. Antigen retrieval: user optimized. Primary antibody: Human IL1 beta antibody. Secondary antibody: Peroxidase goat anti-rabbit at 1:10,000 for 45 min at RT. Localization: cytoplasm. Staining: Close up of medullary lymph node: positive staining in the cytoplasm of circulating macrophages. Neg Ctr (far right) of normal rabbit IgG with pH 6.2 at 40X.
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IL-1B / IL-1 Beta Rabbit anti-Human Polyclonal (N-Terminus) Antibody
Dog, Human, Primate
ELISA, Flo, IF, IHC, IHC-Fr, IHC-P, IP, Neut, RIA, WB
Unconjugated
1 mg/$1,140
IL-1B / IL-1 Beta Antibody - Western Blot (non-reducing) of IL1B / IL-1 Beta antibody. This image was taken for the unconjugated form of this product. Other forms have not been tested.
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IL-1B / IL-1 Beta Rabbit anti-Rat Polyclonal Antibody
Rat
ELISA, WB
Unconjugated
50 µg/$285; 100 µg/$325
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IL-1B / IL-1 Beta Rabbit anti-Sheep Polyclonal (Serum) Antibody
Sheep
ELISA, WB
Unconjugated, Serum
0.1 ml/$475
IL-1B / IL-1 Beta Antibody - IHC of paraffin-embedded muscle tissues using IL1B mouse monoclonal antibody with DAB staining.
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IL-1B / IL-1 Beta Mouse anti-Human Monoclonal (3A6) Antibody
Human
ELISA, IF, IHC, IHC-P, WB
Unconjugated
100 µl/$365
IL-1B / IL-1 Beta Antibody - IHC of paraffin-embedded Adenocarcinoma of Human endometrium tissue using anti-IL1B mouse monoclonal antibody.
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IL-1B / IL-1 Beta Mouse anti-Human Monoclonal (OTI3E1) Antibody
Human
IF, IHC, IHC-P, WB
Unconjugated
100 µl/$345
IL-1B / IL-1 Beta Antibody - Formalin-fixed and paraffin-embedded human lung carcinoma with IL1B Antibody , which was peroxidase-conjugated to the secondary antibody, followed by DAB staining. This data demonstrates the use of this antibody for immunohistochemistry; clinical relevance has not been evaluated.
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IL-1B / IL-1 Beta Rabbit anti-Human Polyclonal (aa148-174) Antibody
Human
Flo, IHC, IHC-P, WB
Unconjugated
400 µl/$325
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IL-1B / IL-1 Beta Mouse anti-Sheep Monoclonal (ID4) Antibody
Goat, Sheep, Bovine
ELISA, Flo, IHC, IHC-Fr
Unconjugated
50 µg/$365; 250 µg/$920
IL-1B / IL-1 Beta Antibody - Western Blot (non-reducing) of IL1B / IL-1 Beta antibody. This image was taken for the unconjugated form of this product. Other forms have not been tested.
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IL-1B / IL-1 Beta Rabbit anti-Mouse Polyclonal Antibody
Mouse
ELISA, WB
Unconjugated
50 µg/$285; 100 µg/$325
IL-1B / IL-1 Beta Antibody - Human peripheral blood mononuclear cells were stimulated with LPS in the presence of Brefeldin A for 4 hours. The cells were surface stained with FITC anti-human CD14 and intracellularly stained with PE anti-human IL-1b.
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IL-1B / IL-1 Beta Mouse anti-Human Monoclonal (CRM56) Antibody
Human
ELISA, Flo, Neut
Unconjugated
50 µg/$225; 500 µg/$335
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IL-1B / IL-1 Beta Goat anti-Human Polyclonal (Biotin) Antibody
Human
ELISA, IHC, WB
Biotin Conjugated
50 µg/$1,005
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IL-1B / IL-1 Beta Mouse anti-Pig Monoclonal (Azide-free) (DF8) Antibody
Pig
WB
Unconjugated, Azide-free
250 µg/$605; 500 µg/$1,095
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IL-1B / IL-1 Beta Rabbit anti-Mouse Polyclonal Antibody
Mouse
ELISA, Neut, WB
Unconjugated
30 µg/$245; 100 µg/$475
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Chicken
7.8 - 500 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Plasma, Serum, Tissue Homogenates
1 Plate/$780
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Rabbit
3.12 - 200 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Plasma, Serum, Tissue Homogenates
1 Plate/$600
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Pig
1.56 - 100 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Plasma, Serum, Tissue Homogenates
1 Plate/$510
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Mouse
6.25 - 400 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Serum
1 Plate/$650
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Dog
7.81 - 500 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Plasma, Serum, Tissue Homogenates
1 Plate/$630
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Bovine
15.63 - 1000 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Plasma, Serum, Tissue Homogenates
1 Plate/$850
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Human
15.63 - 1000 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Plasma, Serum, Tissue Homogenates
1 Plate/$510
IL-1B / IL-1 Beta ELISA Kit
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Sandwich
96-Well Strip Plate
Rat
15.6 - 1000 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Cell Lysates, Plasma, Serum, Tissue Homogenates
1 Plate/$520
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E. coli
None
Biologically active
Less than 0.2 EU/µg protein (determined by LAL method).
17.3 kDa (SDS-PAGE)
50 µg/$395; 10 µg/$235; 1 mg/$2,670
IL-1B / IL-1 Beta Antibody - Western blot of IL-1beta antibody
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IL-1B / IL-1 Beta Rabbit anti-Human Polyclonal (Internal) Antibody
Mouse, Rat, Human
ELISA, WB
Unconjugated
50 µl/$235; 100 µl/$265; 200 µl/$335
IL-1B / IL-1 Beta Antibody - Western blot of recombinant IL1B.  This image was taken for the unconjugated form of this product. Other forms have not been tested.
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IL-1B / IL-1 Beta Guinea pig anti-Rabbit Polyclonal (aa118-268) Antibody
Rabbit
WB
Unconjugated
100 µl/$255; 200 µl/$295; 500 µl/$435; 1 ml/$515
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