The Antiseptic and Antineoplastic Agent Taurolidine Modulates Key Leukocyte Functions.

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Wouters Y, Mennen GRH, Te Morsche RHM, Roelofs HMJ, Wanten GJA

The Antiseptic and Antineoplastic Agent Taurolidine Modulates Key Leukocyte Functions.

In Vivo. 2022 Sep-Oct;36(5):2074-2082. doi: 10.21873/invivo.12933.

PubMed ID
36099103 [ View in PubMed
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Abstract

BACKGROUND/AIM: Although taurolidine is known to exert a wide spectrum of biological actions, its effects on immune cells have not been characterized in detail. In this study, we investigated the ex vivo effects of taurolidine on relevant innate and adaptive immune cell functions. MATERIALS AND METHODS: Leukocyte functions in whole blood were assessed following treatment with various taurolidine concentrations. Viability of peripheral blood mononuclear cells (PBMCs) and granulocytes was measured using the WST-1 assay. PBMC function was assessed by measuring TNFalpha and IFNgamma production after stimulation with lipopolysaccharide (LPS) or Candida, respectively. Reactive oxygen species (ROS) production by granulocytes was measured in whole blood using luminol-enhanced chemiluminescence. Granulocyte degranulation and activation were evaluated by membrane expression of degranulation (CD63, CD66B) and adhesion markers (CD62L, CD11b) using immunofluorescent staining followed by flow-cytometric analysis. RESULTS: Taurolidine decreased viability of PBMCs and granulocytes: after 2 h, IC(50) concentrations were 500 and 520 mug/ml, respectively. Following prolonged exposure (>/=24 h) of PBMCs, the IC(50) concentrations declined to 40 mug/ml. PBMC cytokine production significantly decreased at taurolidine concentrations below the cytotoxic threshold, whereas no changes in ROS production were observed. The expression of all granulocyte adhesion and degranulation markers increased at concentrations higher than 500 mug/ml (the cytotoxic level of taurolidine). CONCLUSION: Taurolidine exhibits a dose- and time-dependent cytotoxicity toward PBMCs and granulocytes. The effects on PBMCs, as exemplified by a decrease in cytokine production, occurred below the toxic threshold, whereas granulocyte function (ROS production) remained unchanged at these taurolidine concentrations. Granulocyte activation and degranulation markers only increased at cytotoxic taurolidine concentrations.

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