| First Author | Wong J | Year | 2014 |
| Journal | Cancer Biol Ther | Volume | 15 |
| Issue | 10 | Pages | 1395-403 |
| PubMed ID | 25046000 | Mgi Jnum | J:325918 |
| Mgi Id | MGI:6878018 | Doi | 10.4161/cbt.29922 |
| Citation | Wong J, et al. (2014) Production of IL-1beta by bone marrow-derived macrophages in response to chemotherapeutic drugs: synergistic effects of doxorubicin and vincristine. Cancer Biol Ther 15(10):1395-403 |
| abstractText | 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-1beta plays a central role as an initiator cytokine in immune responses, we compared doxorubicin, a drug known to induce IL-1beta production, with ten other commonly prescribed chemotherapeutic drugs in their ability to lead to processing and secretion of IL-1beta by primary mouse macrophages. Seven of them (melphalan, cisplatin, vincristine, etoposide, paclitaxel, methotrexate, and cytarabine) caused the production of IL-1beta 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-1beta, IL-6, and CXCL1. The absence of TNF-alpha and IL-1 signaling caused a partial reduction in the production of mature IL-1beta. Three small-molecule inhibitors known to suppress activity of kinases situated upstream of mitogen-activated kinases (MAPKs) inhibited the expression of IL-1beta, 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. |
