Cytokine Storm—Definition, Causes, and Implications

Jarczak, Dominik; Nierhaus, Axel

doi:10.3390/ijms231911740

Cited by 95 publications

(70 citation statements)

References 224 publications

(215 reference statements)

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“…The dysregulated immune response in COVID-19 is associated with an enhanced release of inflammatory mediators [ 38 , 39 , 40 , 41 , 42 , 43 ]. Several studies, however, have challenged the concept of a cytokine storm that would differentiate COVID-19 from sepsis [ 44 , 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Infection with SARS-CoV-2 Is Associated with Elevated Levels of IP-10, MCP-1, and IL-13 in Sepsis Patients

et al. 2023

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Immunothrombosis, an excessive inflammatory response with simultaneous overactivation of the coagulation system, is a central pathomechanism in sepsis and COVID-19. It is associated with cellular activation, vascular damage, and microvascular thrombosis, which can lead to multiple organ failure and death. Here, we characterized factors related to immunothrombosis in plasma samples from 78 sepsis patients. In the course of routine clinical testing, SARS-CoV-2 was detected in 14 of these patients. Viral infection was associated with a higher mortality. Both, COVID-19 negative and COVID-19 positive sepsis patients showed increased levels of effectors of immunothrombosis, including platelet factor 4, D-dimer, nucleosomes, citrullinated histone H3, high mobility group box-1 protein, as well as phosphatidylserine-expressing platelet-derived extracellular vesicles, compared to healthy controls (n = 25). Using a 27-plex cytokine bead array, we found that Interleukin (IL)-1ra, IL-6, IL-8, IL-13, tumor necrosis factor (TNF)-α, interferon inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and granulocyte-colony stimulating factor (G-CSF) were elevated in both, COVID-19 negative and COVID-19 positive sepsis patients, as compared to healthy controls. SARS-CoV-2 infection was associated with elevated levels of IP-10, MCP-1, and IL-13, while all other mediators widely overlapped between COVID-19 negative and COVID-19 positive patients.

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Section: Discussionmentioning

confidence: 99%

Infection with SARS-CoV-2 Is Associated with Elevated Levels of IP-10, MCP-1, and IL-13 in Sepsis Patients

et al. 2023

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“…In sepsis and related diseases, such as severe COVID-19 and malaria, complement system activation is associated with a life-threatening cytokine storm which is caused by an excessive immune response, leading to increased release of cytokines and chemokines such as TNF-α, IFN-γ, IL-1, IL-6, IL-12, IL-18, CCL2, CXCL8, and CXCL10, among others [ 232 , 233 , 234 ]. As mentioned earlier, increased production of these pro-inflammatory cytokines and chemokines has been observed during babesiosis [ 27 , 28 , 30 , 136 , 150 , 160 ].…”

Section: Complement Systemmentioning

confidence: 99%

“…Thus, increased production of pro-inflammatory cytokines and chemokines during canine babesiosis may result from complement activation. However, according to Jarczak and Nierhaus [ 232 ], the chemokine IL-8, as well as the cytokine IL-6, may also be involved in activation of the complement system in the brain by increasing blood–brain barrier permeability, leading to cerebral oedema. This may lead to further pro-inflammatory changes and increased release of pro-inflammatory cytokines and chemokines [ 232 ].…”

Section: Complement Systemmentioning

confidence: 99%

Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines—A Review

Zygner

Gójska-Zygner²,

Norbury

2023

Pathogens

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Canine babesiosis is a tick-borne protozoan disease caused by intraerythrocytic parasites of the genus Babesia. The infection may lead to anemia in infected dogs. However, anemia is not directly caused by the pathogen. The parasite’s developmental stages only have a marginal role in contributing to a decreased red blood cell (RBC) count. The main cause of anemia in affected dogs is the immune response to the infection. This response includes antibody production, erythrophagocytosis, oxidative damage of RBCs, complement activation, and antibody-dependent cellular cytotoxicity. Moreover, both infected and uninfected erythrocytes are retained in the spleen and sequestered in micro-vessels. All these actions are driven by pro-inflammatory cytokines and chemokines, especially IFN-γ, TNF-α, IL-6, and IL-8. Additionally, imbalance between the actions of pro- and anti-inflammatory cytokines plays a role in patho-mechanisms leading to anemia in canine babesiosis. This article is a review of the studies on the pathogenesis of anemia in canine babesiosis and related diseases, such as bovine or murine babesiosis and human or murine malaria, and the role of pro-inflammatory cytokines and chemokines in the mechanisms leading to anemia in infected dogs.

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“…Preliminary results on safety and efficacy were encouraging, but data on long-term follow-up are needed [ 205 ]. The toxicities of the therapy consist mainly of cytokine storm syndrome, that can be life-threatening for patients, although in most cases effective specific strategies can be used that can block released pro-inflammatory cytokines, including the use of monoclonal antibodies that can block IL-6 activity [ 206 ]. In SLE, B-cell depletion is a potentially curative approach, although a complete blockade of antibody production may increase susceptibility to infection.…”

Section: Future Therapiesmentioning

confidence: 99%

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus

Accapezzato

Caccavale

Paroli

et al. 2023

IJMS

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Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the development of effective targeted therapies, that hold out hope for personalized therapy. However, the new drugs available to date are still an adjunct to conventional therapy, which is known to be toxic in the short and long term. The purpose of this review is to summarize recent advances in understanding the pathogenesis of the disease and discuss the results obtained from the use of new targeted drugs, with a look at future therapies that may be used in the absence of the current standard of care or may even cure this serious systemic autoimmune disease.

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Cytokine Storm—Definition, Causes, and Implications

Cited by 95 publications

References 224 publications

Infection with SARS-CoV-2 Is Associated with Elevated Levels of IP-10, MCP-1, and IL-13 in Sepsis Patients

Infection with SARS-CoV-2 Is Associated with Elevated Levels of IP-10, MCP-1, and IL-13 in Sepsis Patients

Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines—A Review

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus

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