Acute cytokine release syndromes are associated with some therapeutic antibodies 
in man, leading to a spectrum of clinical signs from nausea, chills and fever to 
more serious dose limiting hypotension and tachycardia. When anticipated this 
syndrome is typically manageable, however this adverse reaction recently became 
headline news when a massive and unexpected cytokine release syndrome occurred 
within a few hours of dosing six healthy volunteers with a therapeutic antibody, 
putting their lives at risk due to multiple organ failure. Preclinical studies 
did not predict this adverse event, emphasising the need to compare the relative 
potency of the product in man and the chosen toxicology species, so that 
additional margins of safety can be applied when conducting first in man (FIM) 
studies if there is uncertainty over the predictability of the toxicology 
species. In vitro human PBMC and whole blood cultures may be useful for 
predicting cytokine release. However since cytokine release arises through at 
least two distinct mechanisms, it should be emphasised that the utility of these 
in vitro methods needs to be established for each antibody product.