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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 - 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.
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JAK2 Goat anti-Human Polyclonal Antibody
ELISA, Peptide-ELISA
Unconjugated
100 µg/$467
IL1A / IL-1 Alpha Antibody - Human Tonsil: Formalin-Fixed, Paraffin-Embedded (FFPE)
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (1G2) Antibody
Human
IF, IHC, IHC-P, WB
Unconjugated
50 µl/$460
IL1A / IL-1 Alpha Antibody - Anti-IL1 Alpha antibody IHC of human spleen. Immunohistochemistry of formalin-fixed, paraffin-embedded tissue after heat-induced antigen retrieval. Antibody dilution 1:400.
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (3A6F11) Antibody
Human
ELISA, IHC, IHC-P, WB
Unconjugated
50 µl/$440
IL1A / IL-1 Alpha Antibody - IHC of paraffin-embedded Human breast tissue using anti-IL1A mouse monoclonal antibody. (Heat-induced epitope retrieval by 10mM citric buffer, pH6.0, 120°C for 3min).
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (OTI2F8) Antibody
Human
IF, IHC, IHC-P, WB
Unconjugated
100 µl/$450
IL1A / IL-1 Alpha Antibody - IHC of paraffin-embedded Human breast tissue using anti-IL1A mouse monoclonal antibody. (Heat-induced epitope retrieval by 10mM citric buffer, pH6.0, 120°C for 3min).
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (Carrier-free) (OTI2F8) Antibody
Human
IF, IHC, WB
Unconjugated, Carrier-free
100 µg/$511
IL1A / IL-1 Alpha Antibody - Western Blot (non-reducing) of IL1A / IL1 Alpha antibody. This image was taken for the unconjugated form of this product. Other forms have not been tested.
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IL1A / IL-1 Alpha Rabbit anti-Mouse Polyclonal Antibody
Mouse
ELISA, WB
Unconjugated
50 µg/$335; 100 µg/$371
IL1A / IL-1 Alpha Antibody - Western Blot (non-reducing) of IL1A / IL1 Alpha antibody. This image was taken for the unconjugated form of this product. Other forms have not been tested.
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IL1A / IL-1 Alpha Goat anti-Rat Polyclonal Antibody
Rat
ELISA, WB
Unconjugated
50 µg/$335; 100 µg/$371
IL1A / IL-1 Alpha Antibody - Western Blot (non-reducing) of IL1A / IL1 Alpha antibody. This image was taken for the unconjugated form of this product. Other forms have not been tested.
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IL1A / IL-1 Alpha Goat anti-Rat Polyclonal (Biotin) Antibody
Rat
ELISA, WB
Biotin Conjugated
25 µg/$335; 50 µg/$371
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (aa1-112) Antibody
Human
ELISA, WB
Unconjugated
100 µg/$826
IL1A / IL-1 Alpha ELISA Kit
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Sandwich
96-Well Strip Plate
Mouse
1.9 - 125 pg/ml
Colorimetric - 450nm (TMB)
Cell Culture Supernatants, Plasma, Serum, Tissue Homogenates
1 Plate/$649
IL1A / IL-1 Alpha 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/$854
IL1A / IL-1 Alpha Protein - Recombinant Interleukin 1 Alpha By SDS-PAGE
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E. coli
His
16.9 kDa
10 µg/$286; 50 µg/$472; 100 µg/$752; 200 µg/$942; 1 mg/$2,069; 500 µg/$1,600; 5 mg/$3,761
IL1A / IL-1 Alpha Antibody
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal Antibody
Human
ELISA, IHC, WB
Unconjugated
100 µl/$435
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IL1A / IL-1 Alpha Goat anti-Rabbit Polyclonal Antibody
Rabbit
ELISA
Unconjugated
0.1 mg/$533
IL1A / IL-1 Alpha Antibody - Western blot of recombinant IL1A / IL1 Alpha.  This image was taken for the unconjugated form of this product. Other forms have not been tested.
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IL1A / IL-1 Alpha Rabbit anti-Guinea pig Polyclonal (aa111-204) Antibody
Guinea pig
WB
Unconjugated
100 µl/$311; 200 µl/$355; 500 µl/$499; 1 ml/$571
IL1A / IL-1 Alpha ELISA Kit
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Sandwich
96-Well Strip Plate
Monkey
7.8 - 500 pg/ml
Colorimetric - 450nm (TMB)
Plasma, Serum, Tissue Homogenates
1 Plate/$815
IL1A / IL-1 Alpha Antibody - IHC of IL-1 (F8) pAb in paraffin-embedded human lung carcinoma tissue.
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IL1A / IL-1 Alpha Rabbit anti-Human Polyclonal (Phe8) Antibody
Mouse, Rat, Human
IHC, IHC-P
Unconjugated
100 µl/$404
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IL1A / IL-1 Alpha Mouse anti-Mouse Monoclonal (Preservative Free) (Flo1) Antibody
Mouse
ELISA
Unconjugated, Preservative Free
0.1 mg/$570
IL1A / IL-1 Alpha Antibody - IHC of paraffin-embedded Human liver tissue using anti-IL1A mouse monoclonal antibody. (Heat-induced epitope retrieval by 10mM citric buffer, pH6.0, 120°C for 3min).
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (OTI3C3) Antibody
Human
IF, IHC, IHC-P, WB
Unconjugated
100 µl/$419
IL1A / IL-1 Alpha Antibody - IHC of paraffin-embedded Human liver tissue using anti-IL1A mouse monoclonal antibody. (Heat-induced epitope retrieval by 10mM citric buffer, pH6.0, 120°C for 3min).
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (Carrier-free) (OTI3C3) Antibody
Human
IF, IHC, WB
Unconjugated, Carrier-free
100 µg/$483
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IL1A / IL-1 Alpha Rabbit anti-Mouse Monoclonal (Preservative Free) (148) Antibody
Mouse
ELISA
Unconjugated, Preservative Free
50 µl/$300; 100 µl/$360; 1 ml/$1,201
IL1A / IL-1 Alpha Antibody - IHC of paraffin-embedded Human pancreas tissue using anti-IL1A mouse monoclonal antibody. (Heat-induced epitope retrieval by 10mM citric buffer, pH6.0, 120°C for 3min).
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IL1A / IL-1 Alpha Mouse anti-Human Monoclonal (OTI2F11) Antibody
Human
IF, IHC, IHC-P, WB
Unconjugated
100 µl/$434
IL1A / IL-1 Alpha Antibody - Immunochemical staining of mouse IL1A in mouse liver with rabbit polyclonal antibody at 1:500 dilution, formalin-fixed paraffin embedded sections.
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IL1A / IL-1 Alpha Rabbit anti-Mouse Polyclonal (Preservative Free) Antibody
Mouse
IHC-P
Unconjugated, Preservative Free
50 µl/$285; 100 µl/$322; 200 µl/$360
IL1A / IL-1 Alpha Antibody - Western blot of IL1A / IL-1 Alpha antibody.
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IL1A / IL-1 Alpha Rabbit anti-Dog Polyclonal (aa94-262) Antibody
Dog
WB
Unconjugated
100 µl/$311; 200 µl/$355; 500 µl/$499; 1 ml/$571
IL1A / IL-1 Alpha Antibody - Formalin-fixed and paraffin-embedded human lung carcinoma reacted with IL1A 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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IL1A / IL-1 Alpha Rabbit anti-Human Polyclonal (aa177-206) Antibody
Human
Flo, IHC, IHC-P, WB
Unconjugated
400 µl/$386
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