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• W2083432026 abstract "Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely employed to treat a variety of cancers in patients but often lead to serious symptoms that negatively affect physical functioning and quality of life. There is compelling evidence that implicates cytotoxic chemotherapy-induced inflammation in the etiology of these symptoms. Because IL-1β plays a central role as an initiator cytokine in immune responses, we compared doxorubicin, a drug known to induce IL-1β production, with ten other commonly prescribed chemotherapeutic drugs in their ability to lead to processing and secretion of IL-1β by primary mouse macrophages. Seven of them (melphalan, cisplatin, vincristine, etoposide, paclitaxel, methotrexate, and cytarabine) caused the production of IL-1β in cells pretreated with lipopolysaccharide. When delivered in combination with doxorubicin, one of the drugs, vincristine, was also capable of synergistically activating the NLRP3-dependent inflammasome and increasing expression of IL-1β, IL-6, and CXCL1. The absence of TNF-α and IL-1 signaling caused a partial reduction in the production of mature IL-1β. Three small-molecule inhibitors known to suppress activity of kinases situated upstream of mitogen-activated kinases (MAPKs) inhibited the expression of IL-1β, IL-6, and CXCL1 when doxorubicin and vincristine were used singly or together, so specific kinase inhibitors may be useful in reducing inflammation in patients receiving chemotherapy." @default.
• W2083432026 created "2016-06-24" @default.
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• W2083432026 date "2014-07-21" @default.
• W2083432026 modified "2023-10-18" @default.
• W2083432026 title "Production of IL-1β by bone marrow-derived macrophages in response to chemotherapeutic drugs" @default.
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• W2083432026 doi "https://doi.org/10.4161/cbt.29922" @default.
• W2083432026 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4130732" @default.
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