Cytokine release syndrome

Reference work entry




Cytokine release syndrome commonly complicates first infusions of certain therapeutic monoclonal antibodies which have lymphocyte mitogenic properties in vitro. Agents with which CRS has been described include OKT3 (anti-CD3), CAMPATH (anti-CD52), and rituximab (anti-CD20). CRS is characterized clinically by hypothermia or fever, rigors, hypotension, rash, dyspnea and occasionally bronchospasm, rash, nausea and diarrhea. These side effects develop soon after the administration of the agent and can last for several hours. Typically discontinuing the drug and employing supportive measures leads to recovery. However, severe and even fatal reactions associated with pulmonary edema and hepatitis have been described. The clinical syndrome is caused by a sudden increase in TNF-α, IFN-γ, and IL-6 release. The CRS potential of biological agents can be predicted by the presence of mitogenicity and induction of TNF-α and IFN-γ release in whole blood cultures exposed to...

This is a preview of subscription content, log in to check access.


  1. Matthys P, Dillen C, Proost P, et al (1993) Modification of the anti-CD3-induced cytokine release syndrome by anti-interferon-gamma or anti-interleukin-6 antibody treatment: protective effects and biphasic changes in blood cytokine levels. Eur J Immunol 23:2209–16PubMedGoogle Scholar
  2. Wing MG, Waldmann H, Isaacs J, et al (1995) Ex-vivo whole blood cultures for predicting cytokine-release syndrome: dependence on target antigen and antibody isotype. Therap Immunol 2:183–90Google Scholar
  3. Winkler U, Jensen M, Manzke O, et al (1999) Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 94:2217–24PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004