Cytokine storm is a condition characterized by high plasma levels of inflammatory cytokines, chemokines and interferons which can be commonly induced by pathogens or their components (endotoxin, lipoproteins, DNA, RNA etc ). Cytokine storm can also be induced in response to certain drugs (e.g. recombinant proteins, therapeutic antibodies, macromolecular nucleic acid-based therapeutics). It is accompanied by fever, hypo- or hypertension and may progress to a more severe life-threatening condition called systemic inflammatory response syndrome (SIRS). For example, cytokine storm was severe side effect in phase I clinical trial of experimental monoclonal antibody therapeutics TGN1412, which resulted in 6 healthy donor volunteers enrolled into the study becoming critically ill and requiring intense care (1). All patients had high serum levels of TNFa, IFNg and other pro-inflammatory messengers (1).  Cytokine storm to this drug was not observed in preclinical studies involving rats and cynomolgus monkeys (1) but was easily detectable in vitro using cytokine release assay in human primary blood cells (2). Nanoparticles can be used for delivery of therapeutic proteins, antibodies and nucleic acids, or contain biologicals (antibodies, proteins or nucleic acids) as targeting agents. In addition, some nanoparticles can be made of biological molecules (e.g.  self-assembling peptides or siRNAs). These details warrant studying both nanotechnology platforms and their macromolecular payload and targeting agents for the ability to induce inflammatory cytokines. Human whole blood and peripheral blood mononuclear cells (PBMC) are considered reliable and predictive model for this purpose. The data obtained from such in vitro studies is intended to supplement other preclinical data to create nanoparticle safety profile and ensure transition of nanomedicines toward clinical development.

• NCL_Method_ITA-10_May2020.pdf(PDF | 420 KB)

Researchers should cite this work as follows:

• Timothy Potter, Edward Cedrone, Barry Neun, Marina Dobrovolskaia (2020). NCL Method ITA-10. (Version 2.0). NCI Hub. doi:10.17917/GBQR-BN14

  BibTex | EndNote

1. chemokines
2. cytokines
3. interferons
4. Nanoparticles