@article{c2721c866c1e4d53a2a03cfbc1caa84f,
title = "Tumor necrosis factor-α in cisplatin nephrotoxicity: A homebred foe?",
abstract = "A robust inflammatory response involving tumor necrosis factor-α (TNFα) is induced during cisplatin nephrotoxicity. Using chimeric models, Reeves and colleagues now demonstrate that resident kidney cells, rather than infiltrating immune cells, are the major producers of TNF-α. Blockade of TNFα attenuates inflammation and associated kidney injury.",
author = "Z. Dong and Atherton, {S. S.}",
note = "Funding Information: Although negating a role of bone marrow-derived immune cells in TNF-α production, the study by Reeves and colleagues 5 does not exclude the involvement of these cells in cisplatin nephrotoxicity. Recent work by Rabb and colleagues 6 demonstrated that, as compared with wild-type animals, T cell-deficient mice were more resistant to cisplatin nephrotoxicity. Notably, reconstitution of Tcells into these animals partially restored their sensitivity to cisplatin injury. 6 Thus, immune cells, particularly the infiltrating Tcells, contribute to the development of renal pathology during cisplatin treatment. Intriguingly, Rabb and colleagues also demonstrated that the production of proinflammatory cytokines, including TNF-α, was attenuated in T cell-deficient mice, suggesting a role for T cells in triggering inflammation and TNF-α production during cisplatin nephrotoxicity. 6 Apparently, there is a discrepancy between the study by Reeves and colleagues and the study by Rabb's group: the former indicates TNF-α production by resident kidney cells, 5 whereas the latter suggests the involvement of infiltrating T cells. 6 How can these findings be reconciled? One possibility is that, although TNF-α is produced mainly by resident kidney cells, infiltrating T cells may have a regulatory or stimulatory role. This scenario is supported by the observation that Tcell infiltration occurs very early (within hours) during cisplatin nephrotoxicity. 6 Is there indeed a functional interaction between infiltrating T cells and resident kidney cells that leads to TNF-α production? How do T cells regulate TNF-α production in kidney cells? Do they secrete cytokines to prime these cells? What specific cytokines do they produce? These are important questions for investigation in the future. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2007",
month = jul,
doi = "10.1038/sj.ki.5002320",
language = "English (US)",
volume = "72",
pages = "5--7",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "1",
}