Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 7 No. 2 March 27, 2020 p.105-114
Original Article
Evaluation of cytokine storms in a disseminated intravascular coagulation monkey model
  • Yoshitaka Hirasawa (Ina Research Inc. /
Yoshitaka Hirasawa 1) , Atsushi Fujiwara 1) , Kazuya Tabata 1) , Kenji Yoshida 2) , Tsutomu Negama 2) , Takayuki Anzai 3) , Shin-ichi Sato 1)
1) Ina Research Inc. , 2) Sekisui Medical Co., Ltd. , 3) Showa University School of Medicine
Keywords: Disseminated intravascular coagulation (DIC), Cytokine storm, Cytokine release syndrome, Cynomolgus monkey

The purpose of this study was to profile cytokine storms (cytokine release syndrome) in the LPS-induced disseminated intravascular coagulation (DIC)-cynomolgus monkey model by measuring changes in 22 cytokines using Luminex. In this study, increases were noted in 20 cytokines, excluding IL-4 and IL-17A. Specifically, IL-6, IL-8, G-CSF and TNF-α, pro-inflammatory cytokines, and IL-10, an anti-inflammatory cytokine, as well as MCP-1, markedly increased by 10,000 pg/mL or more. In addition to the marked increases in the pro-inflammatory cytokines IL-6 and G-CSF, the concentrations of IL-5, IL-18, IFN-γ, VEGF and IL-15 increased continuously. Also, in addition to the marked increases in the pro-inflammatory cytokine IL-8 as well as in MCP-1, the concentrations of IL-1ra, IL-2, IL-1β, IL-12/23 (p40), GM-CSF and TGF-α gradually decreased after initially increasing. On the other hand, in addition to the marked increases in the pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10, MIP-1β and MIP-1α transiently increased and then rapidly disappeared from serum. IL-13 increased at 6 hr after administration only. Since the behavior of cytokines in this monkey model was similar to those noted in DIC in humans, this model will be useful for evaluating the efficacy of anti-DIC drugs. In addition, this model will also be useful for assessing the risk of cytokine storm development, which is a serious adverse effect of certain types of antibody drugs and CAR-T cell-based therapies.