Time- and dose-dependent inhibition of neutrophil extracellular trap formation by blocking of the interleukin-1 receptor

Autor: Hannah Wadehn, Laia Pagerols Raluy, Jan Kolman, Charlotte Duecker, Magdalena Trochimiuk, Birgit Appl, Michael Boettcher, Konrad Reinshagen, Julian Trah
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Central European Journal of Immunology, Vol 46, Iss 4, Pp 419-426 (2021)
Druh dokumentu: article
ISSN: 1426-3912
1644-4124
DOI: 10.5114/ceji.2021.111493
Popis: 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.
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