TY - JOUR JO - Central European Journal of Immunology SN - 1426-3912 VL - 46 IS - 4 PY - 2021 ID - Wadehn2021 TI - Time- and dose-dependent inhibition of neutrophil extracellular trap formation by blocking of the interleukin-1 receptor AB - Besides performing phagocytosis and degranulation, neutrophils are capable of eliminating microorganisms by releasing neutrophil extracellular traps (NETs). NET formation was found to be associated with increased mortality in sepsis. During sepsis levels of interleukin 1 (IL-1), a cytokine, increases significantly and also was associated with increased mortality. Blocking of the interleukin 1 (IL-1) receptor by anakinra leads to less NET formation in gout patients. However, NET formation is crucial during infection by trapping pathogens and thereby slowing the process. Total or early blocking of cascades leading to NETs may lead to aggravation of infection in otherwise mild cases. The dose- and time-dependent effect of the IL-1 receptor antagonist anakinra was tested on spontaneous, lipopolysaccharide (LPS)-induced and phorbol-12-myristate 13-acetate (PMA)-induced formation of NETs in vitro . Quantitative detection of NETs was performed for NETspecific proteins and cell-free DNA. Immunostained microscopy imaging was used for visualization. Our study shows a dose- and time-dependent inhibitory effect of anakinra that involves the change of intracellular calcium mobilization on the formation of NETs in vitro for PMA-stimulated neutrophils but not for LPS-stimulated neutrophils. It may be useful for treatment of sepsis as part of a multimodal treatment concept, but it seems that timing and dose need to be carefully chosen. AU - Wadehn, Hannah AU - Pagerols Raluy, Laia AU - Kolman, Jan AU - Duecker, Charlotte AU - Trochimiuk, Magdalena AU - Appl, Birgit AU - Boettcher, Michael AU - Reinshagen, Konrad AU - Trah, Julian SP - 419 EP - 426 DA - 2021 DO - 10.5114/ceji.2021.111493 UR - http://dx.doi.org/10.5114/ceji.2021.111493 ER -