Cytokine-release syndromes

Cytokine-release syndrome, also known as cytokine-release syndrome, is an undesirable side effect(ADR) caused by the systemic application of various drugs or other therapeutic measures that induce massive cell decay.

The cytokine-release syndrome is considered an "infusion reaction". The ADR is caused by a sudden release of cytokines such as TNF-alpha, IL-8, IL-6 (Barker CA et al. 2018), triggered by massive decay of immune or tumor cells. The cytokine IL-6 is believed to play a central role in this process.

The syndrome was described after application

• of various biologicals such as rituximab, tocilizumab, alemtuzumab, basiliximab, muromonab-CD3 (Lichtenstein L et al. 2015)
• after a CAR-T cell therapy
• after versch. Chemotherapeutics
• after radiotherapy - very rarely - (Barker CA et al. 2018)

Clinically, this ADR is characterized by varying degrees of body reactions such as fever, nausea, chills, arterial hypotension, tachycardia, asthenia, headache, macular exanthema and dyspnoea (Vultaggio A et al. 2014). The clinical presentation may well correspond to an IgE-mediated immediate type response (Lee DW et al. 2015)

Massive reactions up to a cytokine storm often occur during the first treatment, especially in hematological diseases. They can be life-threatening.

The following degrees of severity can be distinguished (Porter D et al. 2018):

• Grade 1 (only symptomatic therapy required)
• Grade 2 (moderately intensive treatment necessary)
• Grade 3 (aggressive therapy necessary)
• Grade 4 (life-threatening)
• Grade 5 (with death consequences)

The therapeutic ones are to be aligned according to the trigger and severity. For rheumatic diseases, antihistamines, glucocorticoids or NSAIDs can be given as a preventive measure. Depending on the severity of the disease, immunosuppression can be administered in varying degrees. For grade 4 and 5 reactions, intensive medical measures are necessary.

1. Barker CA et al (2018) Cytokine release syndrome after radiation therapy: case report and review of the literature. J Immunother Cancer 6:1.
2. Lichtenstein L et al (2015) Infliximab-Related Infusion Reactions: Systematic Review. J Crohn's colitis 9:806-815.
3. Porter D et al (2018) Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol 11: 35
4. Vultaggio A et al (2014) Hypersensitivity reactions to biological agents. Immunol Allergy Clin North Am 34:615-632