Interleukin-6-Mediated Inflammation May Cause Methotrexate-Induced Leukoencephalopathy.

Abstract

Children with leukemia treated with methotrexate (MTX) may develop MTX-induced leukoencephalopathy, which can present as seizures or focal neurological deficits. However, the precise pathophysiology has not been fully elucidated. Differences in cytokine/chemokine profiles in cerebrospinal fluid (CSF) between children with MTX-induced leukoencephalopathy and those with posterior reversible encephalopathy syndrome (PRES), an acute neurological condition associated with hypertension, were investigated. Interleukin (IL)-1β, 2, 4, 5, 6, 7, 8, 10, 12, 13, and 17, tumor necrosis factor-alpha, interferon-gamma, granulocyte monocyte colony-stimulating factor, granulocyte colony-stimulating factor, macrophage inflammatory protein-1β, and monocyte chemoattractant protein-1 concentrations were measured in CSF supernatants from 3 children with acute leukemia with MTX-induced leukoencephalopathy, 3 children with acute leukemia with PRES, 6 children with acute leukemia without neurological complications, and 8 children with acute encephalopathy. CSF IL-6 concentrations were higher in children with MTX-induced leukoencephalopathy than in children with acute leukemia with PRES, with acute leukemia without neurological complications, and with acute encephalopathy. We concluded that IL-6 may be involved in the pathogenesis of MTX-induced leukoencephalopathy.

• Authors: Takeshi Asano, Akihiro Iguchi, Taku Miyasho
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 40 Issue 7 Pg. 341-348 (07 2020) ISSN: 1557-7465 [Electronic] United States
• PMID: 32614271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• IL6 protein, human
• Interleukin-6
• Methotrexate

Topics

• Antimetabolites, Antineoplastic (adverse effects)
• Child
• Humans
• Hypertension (cerebrospinal fluid, complications, drug therapy)
• Inflammation (cerebrospinal fluid, complications, drug therapy)
• Interleukin-6 (cerebrospinal fluid, metabolism)
• Leukoencephalopathies (cerebrospinal fluid, complications, drug therapy)
• Methotrexate (adverse effects)
• Posterior Leukoencephalopathy Syndrome (cerebrospinal fluid, complications, drug therapy)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (cerebrospinal fluid, drug therapy)