Cytokine Release Syndrome

A severe immune reaction characterized by excessive release of CYTOKINES. Symptoms include DYSPNEA; FEVER; HEADACHE; HYPOTENSION; NAUSEA; RASH; TACHYCARDIA; HYPOXIA; HYPERFERRITINEMIA, and MULTIPLE ORGAN FAILURE. It is associated with viral infections, SEPSIS; AUTOIMMUNE DISEASES and a variety of factors used in IMMUNOTHERAPY.

Also Known As:

Networked: 4315 relevant articles (240 outcomes, 323 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	COVID-19
2.	Infections
3.	Neoplasms (Cancer)
4.	Inflammation (Inflammations)
5.	Pneumonia (Pneumonitis)

Experts

1.	Grupp, Stephan A: 26 articles (01/2022 - 04/2013)
2.	Teachey, David T: 21 articles (01/2022 - 04/2013)
3.	June, Carl H: 17 articles (01/2022 - 04/2013)
4.	Maude, Shannon L: 17 articles (01/2022 - 06/2013)
5.	Lacey, Simon F: 14 articles (01/2022 - 10/2014)
6.	Levine, Bruce L: 13 articles (01/2022 - 04/2013)
7.	Chavez, Julio C: 12 articles (10/2022 - 01/2017)
8.	Neelapu, Sattva S: 12 articles (10/2022 - 01/2017)
9.	Porter, David L: 12 articles (11/2020 - 04/2013)
10.	Turtle, Cameron J: 11 articles (12/2022 - 11/2017)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Cytokine Release Syndrome:

1.	CytokinesIBA 01/01/2019 - "While highly efficacious, post-infusion T cell activity often results in massive cytokine release precipitating cytokine release syndrome (CRS), the signature toxicity of CAR T cells. " 07/01/2021 - "Hemoadsorption with Cytosorb has proven to be effective in reducing cytokines and possibly in attenuating the devastating effects of the cytokine storm originating from the immune over-response to the initial insult. " 07/26/2022 - "According to previous clinical studies, serum cytokine measurement is helpful for rapid diagnosis of HLH and the differentiation of HLH from other diseases caused by hypercytokinemia, and it perfoms well to clarify subtypes of HLH, to stratify patients with different risks and to predict the prognosis and outcome. " 12/01/2023 - "As the sole documented static mixer-integrated conduit capable of selectively eliminating cytokines at their physiological concentrations, it holds promise in the clinical potential for hypercytokinemia in high-risk patients. " 01/01/2023 - "Real-time monitoring of cytokines in vivo is helpful for assessing the immune status of patients and providing an early warning of a cytokine storm. "
2.	tocilizumab (atlizumab)FDA Link 01/01/2023 - "The patient experienced Grade IV cytokine release syndrome (CRS) and went into complete remission (CR) after anti-inflammatory treatment including tocilizumab. " 01/01/2020 - "Anti-IL-6 may interfere with cytokine storm in severe cases and use of tocilizumab has had good results in a small cohort. " 01/01/2020 - "Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. " 10/16/2014 - "Severe cytokine-release syndrome, which developed in 27% of the patients, was associated with a higher disease burden before infusion and was effectively treated with the anti-interleukin-6 receptor antibody tocilizumab. " 01/01/2023 - "Prompt and aggressive tocilizumab treatment could be protective against the negative consequences of cytokine release syndrome."
3.	Interleukin-6 (Interleukin 6)IBA 01/01/2022 - "In the absence of IL-6 antagonists, anti-inflammatory and immunosuppressive therapeutic strategies, and cytotoxic clearance of cells responsible for hypercytokinemia could be adopted." 01/01/2020 - ", a specific IL-6 inhibitor, led to dramatic clinical improvement in a young patient with severe COVID-19-associated cytokine release syndrome." 11/04/2023 - "Previous studies have focused more on mild and long-term IL-6 elevation, but less on the effects of this short-term IL-6 inflammatory cytokine storm. " 05/25/2022 - "JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-α and IL-6 and have shown various results in clinical trials. " 10/26/2021 - "Interleukin-6 (IL-6) is involved in COVID-19-associated cytokine storm, and several trials investigated whether its inhibition could improve patients' outcome. "
4.	Chimeric Antigen ReceptorsIBA 12/01/2021 - "CD19-target chimeric antigen receptor (CAR)-T cell therapy is highly effective for relapsed/refractory (R/R) acute lymphoblastic leukaemia (ALL), but is often complicated by cytokine release syndrome (CRS), which is potentially life-threatening. " 12/01/2021 - "Despite the impressive efficacy of chimeric antigen receptor (CAR) T-cell therapy, adverse effects, including cytokine release syndrome and neurotoxicity, impede its therapeutic application, thus making the modulation of CAR T-cell activity a priority. " 12/15/2022 - "The Chimeric Antigen Receptor (CAR) T Cell Safety Database Project explored the use of cross-study safety data to identify risk factors associated with severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) after CAR T cell administration. " 01/01/2017 - "Trials with second generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but are associated with risk of cytokine release syndrome (CRS). " 01/01/2023 - "Cytokine release syndrome (CRS) and consumptive coagulopathy can complicate the treatment with chimeric antigen receptor T (CAR-T) cells. "
5.	Antiviral Agents (Antivirals)IBA 01/01/2020 - "The virus may invade the nervous system directly or induce a massive immune inflammatory response via a "cytokine storm." Specific antiviral drugs are still under study. " 01/01/2023 - "Collectively, the results suggest that the IFN cocktail restricts the progression of acute ASF by inducing high levels of ISGs, contributing to the pre-establishment of antiviral status, and modulating the balance of pro- and anti-inflammatory mediators to lessen cytokine storm-mediated tissue damage." 12/01/2022 - "This review first provides an insight into the mechanism of cytokine storm development, as it is directly related to the exhaustion of T cell population, essential for viral clearance and long-term antiviral immunity. " 09/13/2022 - "Multi-Condition QSAR Model for the Virtual Design of Chemicals with Dual Pan-Antiviral and Anti-Cytokine Storm Profiles." 01/01/2022 - "However, SARS-CoV-2 subtly interrupts the equations of immune responses, disrupting the cytolytic antiviral effects of NK cells, while seriously activating infected macrophages and other immune cells to induce an unleashed "cytokine storm", a dangerous and uncontrollable inflammatory response causing life-threatening symptoms in patients. "
6.	Dexamethasone (Maxidex)FDA LinkGeneric 02/04/2022 - "-adjusted monotherapy with dexamethasone was found to be effective; this may be attributed to some DMARDs being unsuitable for cytokine storms, that is, some DMARDs may cause complications in cytokine storms. " 01/01/2023 - "Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome." 01/01/2022 - "The liposomal dexamethasone was mainly distributed into the monocyte/macrophages as a major cell population for inducing the cytokine storm in the lungs. " 12/01/2021 - "We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. " 12/01/2021 - "We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. "
7.	SteroidsIBA 05/01/2010 - "Intrapatient dose escalation with steroid pre-medication appeared effective in reducing symptoms of cytokine release syndrome and the maximum-tolerated dose with this dosing schema was 12 mg/kg/week. " 01/01/2023 - "Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. " 10/20/2021 - "No patients experienced ≥ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to ≤ grade 1 within 72 hours with steroids. " 10/01/2020 - "The treatment of the serious, cytokine storm syndrome and the role of steroids must be elucidated as soon as it is feasible. " 10/01/2020 - "There was divergence regarding the use of steroids in a cytokine storm among the physicians, with only 39% of consultants planning to use steroids whereas about 50% of junior residents and 79% of junior consultants were planning to use the drug. "
8.	Oxygen (Dioxygen)IBA 11/01/2016 - "Active treatment with PMX-DHP and CHDF was helpful in the reduction of days on inhaled oxygen and tracheal intubation in preterm SIRS infants with hypercytokinemia. " 02/01/2021 - "The death rate is undoubtedly correlated with the cytokine storm and other pathological pulmonary characteristics, as a result of which the lungs cannot provide sufficient oxygen to the body's vital organs. " 01/01/2021 - "In theory, however, optimal life-saving potential is thought to occur when LDRT is applied prior to the cytokine storms and before the patients are placed on mechanical oxygen ventilators. " 01/01/2022 - "Six patients (60%) were discharged and remained off oxygen, whereas four progressed and died (1 due to sepsis and 3 in cytokine storm). " 01/01/2022 - "The therapy has been initiated in an attempt to alleviate the prevalent cytokine storm and to prevent intubation and invasive mechanical ventilation, when a long-term nasal oxygen therapy with a maximum flow rate of 8L/min was insufficient to achieve an adequate oxygenation. "
9.	Adrenal Cortex Hormones (Corticosteroids)IBA 04/01/2022 - "Recent reports suggested the efficacy of pulse corticosteroids in stopping the cytokine storm in people infected with SARS-CoV-2, but limited data exists regarding its use in pregnant women. " 07/01/2023 - "The presence of factors such as cytokine release syndrome, the direct effect of the virus on cells through different receptors, and the side effects of current treatments such as corticosteroids are some of the important mechanisms in the occurrence of these alterations. " 03/01/2023 - "The use of corticosteroids in patients with AE caused by a cytokine storm, which is recommended in the AE GL 2016, had already been implemented in most institutions by 2015. " 12/01/2022 - "Corticosteroids serve an immunomodulatory function in the post-viral hyper-inflammatory condition (the cytokine storm, or release syndrome), suppressing the excessive immunological response and preventing multi-organ failure and death. " 05/19/2021 - "Corticosteroids have been the mainstay in treating the cytokine storm caused by the virus. "
10.	AntibodiesIBA 12/01/2009 - "Although these antibodies are effective in pre-clinical and clinical studies, they are costly and have occasionally been associated with adverse effects such as autoimmunity and cytokine storm. " 03/12/2023 - "No cytokine storm and no formation of antibodies to CYT107 were observed. " 01/01/2022 - "A major issue preventing to make full use of the potential of these immunomodulatory antibodies are the severe side-effects, ranging from systemic cytokine release syndrome to organ-specific toxicities. " 01/01/2021 - "The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. " 01/01/2021 - "Transplacental COVID Antibodies and Cytokine Storm in Newborn: Presence of Antibodies does not Indicate Protection Always!"

Therapies and Procedures

1.	Therapeutics 01/01/2023 - "Despite cell-based therapy representing a substantial promise for patients with very limited treatment options, some limitations for its widespread use in the clinical setting remain, including restricted indications, highly complex manufacturing processes, elevated production costs, the lability of cellular products over time, and the potential safety concerns related to the intrinsic characteristics of living cells, including the risk of severe or life-threatening toxicities, such as CAR-T induced neurotoxicity and cytokine release syndrome (CRS). " 03/01/2020 - "Many patients have achieved complete response or remission despite failing multiple previous lines of therapy, but some patients endure the severe risks of cytokine release syndrome, neurotoxicity, and other immunologic effects. " 01/01/2020 - "Here, we report three male patients with R/R classical MCL, who received CD19-directed 4-1BB CAR-T therapy and achieved complete remission, showed mild symptoms of cytokine-release syndrome (CRS) and had no neurological toxicity. " 07/01/2019 - "Although the new therapy offers a promise for patients with advanced disease, it is associated with adverse events including neurotoxicity and cytokine release syndrome, which can be fatal and may require a high level of multidisciplinary supportive care. " 01/01/2021 - "Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. "
2.	Immunotherapy 11/14/2023 - "Systemic immunotherapies cause severe autoimmune toxicities and cytokine storms. " 01/01/2023 - "However, CAR-T cell therapy can lead to immunotherapy-associated side effects including cytokine release syndrome and neurotoxicity. " 02/01/2022 - "Effective control of severe immune-related adverse events, including cytokine release syndrome (CRS), is essential for the success of immunotherapy. " 01/01/2022 - "Cytokine release syndrome (CRS) is a strong immune system response that can occur as a result of the reaction of a cellular immunotherapy with malignant cells. " 01/01/2022 - "Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. "
3.	Hemodiafiltration 10/01/2001 - "After plasma exchange and continuous hemodiafiltration were started, hypercytokinemia and vital signs improved dramatically. " 11/01/2021 - "Continuous Hemodiafiltration with the oXiris Filter Ameliorates Cytokine Storm and Induces Rapid Clinical Improvement in COVID-19 - A Case Report." 02/01/2009 - "To examine the role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the efficacy of continuous hemodiafiltration in the treatment of TLS. " 01/01/2015 - "Continuous hemodiafiltration (CHDF) is used as renal replacement therapy for critically ill patients with renal failure, and to treat hypercytokinemia. " 04/01/2014 - "Efficacy of series double continuous hemodiafiltration using two polymethyl methacrylate membrane hemofilters for patients with hypercytokinemia."
4.	Transplantation 11/01/2021 - "Haploidentical related donor transplantation (haplo-HCT) is associated with cytokine release syndrome (CRS). " 01/01/2021 - "He had CR2 after he experienced grade II cytokine release syndrome of the second CAR-T and underwent umbilical cord blood transplantation. " 12/01/2020 - "MSCs are able to engraft to the damaged tissues after transplantation and promote tissue regeneration, besides MSCs able to secrete immunomodulatory factors that suppress the cytokine storms. " 12/01/2020 - "Cytokine storm is frequently mentioned in connection to medical interventions such as transplantation or administration of drugs. " 08/01/2019 - "She went on to develop cytokine storm shortly following transplantation, with marked T-cell proliferation coincident with myeloid engraftment. "
5.	Plasma Exchange 01/01/2021 - "Therapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release syndrome; a retrospective propensity matched control study." 01/01/2023 - "During the pandemic, therapeutic plasma exchange (TPE) was used to reduce the cytokine storm in the circulation and delay or prevent ICU admissions. " 08/01/2022 - "Role of therapeutic plasma exchange in the management of COVID-19-induced cytokine storm syndrome." 10/01/2001 - "After plasma exchange and continuous hemodiafiltration were started, hypercytokinemia and vital signs improved dramatically. " 12/01/2020 - "Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19."