Cytokine Release Syndrome



Systemic Release of Inflammatory Mediators Usually on First Exposure to a Therapeutic Monoclonal Antibody

  • TNF-α Release
  • Interferon-Gamma Release
  • Interleukin-6 (IL-6) Release
  • Lymphocyte Activation
    • B-Cells
    • T-Cells
    • NK Cells: may play a role in anti-CD3 and alemtuzumab-related cases
  • Myeloid Cell Activation
    • Dendritic Cells
    • Macrophages
    • Monocytes

Potential Mechanisms

  • Direct binding of Monoclonal Antibody to its Ligand on Target Cell Leading to Signaling Within the Cell
    • Cytokine Release by the Target Cell
    • Probably represents the mechanism by which Anti-CD28 superantigens cause cytokine release syndrome: these superantigens are believed to activate T-cells without the primary signal occurring through the T-cell receptor
  • Binding of Fc End of Monoclonal Antibody to Fc Receptors on Non-Target Cells Leading to Signaling Within the Non-Target Cell
    • Cytokine Release by Non-Target Cell
  • Binding of Monoclonal Antibody to Fc Receptor Leading to Clustering and Signaling Within the Target Cell

Cytokine Release Syndrome Grading System (Modified from National Cancer Institute Common Terminology Criteria for Adverse Events, CTCAE v4.0 System) [MEDLINE]

Clinical Manifestations

General Comments

Cardiovascular Manifestations

Dermatologic Manifestations

Gastrointestinal Manifestations

Hematologic Manifestations

Neurologic Manifestations

Pulmonary Manifestations

Renal Manifestations

Other Manifestations


Supportive Care

Hemodynamic Support

Respiratory Support

General Comments

Grade 1 Cytokine Release Syndrome

Grade 2 Cytokine Release Syndrome

Immunosuppressive Treatment (see below)

Grade 3-4 Cytokine Release Syndrome

Immunosuppressive Treatment (Recommended)