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An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy

Long-term treatment with the fungal metabolite drug FTY720 (Fingolimod) was shown to be highly effective in controlling viral immunopathological lesions. However, in this report we show that the anti-inflammatory effect of FTY720 in herpes simplex virus-1 (HSV-1) induced ocular inflammation is lost...

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Autores principales: Reddy, Pradeep B. J., Sehrawat, Sharvan, Suryawanshi, Amol, Rajasagi, Naveen K., Khatri, Madhu, Rouse, Barry T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028216/
https://www.ncbi.nlm.nih.gov/pubmed/24846129
http://dx.doi.org/10.1371/journal.pone.0098051
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author Reddy, Pradeep B. J.
Sehrawat, Sharvan
Suryawanshi, Amol
Rajasagi, Naveen K.
Khatri, Madhu
Rouse, Barry T.
author_facet Reddy, Pradeep B. J.
Sehrawat, Sharvan
Suryawanshi, Amol
Rajasagi, Naveen K.
Khatri, Madhu
Rouse, Barry T.
author_sort Reddy, Pradeep B. J.
collection PubMed
description Long-term treatment with the fungal metabolite drug FTY720 (Fingolimod) was shown to be highly effective in controlling viral immunopathological lesions. However, in this report we show that the anti-inflammatory effect of FTY720 in herpes simplex virus-1 (HSV-1) induced ocular inflammation is lost upon the discontinuation of treatment and lesions rapidly recurred. The lesions that developed after FTY720 treatment withdrawal involved mainly Th17 cells rather than Th1 cells explained in part by differential expression of surface CD103, an integrin that permits migration of effector cells to inflammatory sites. The expression of IL-6, a proinflammatory cytokine involved in the generation of Th17 cells, was found to be increased in FTY treated mice as compared to controls and this effect could be abrogated upon administration of neutralizing antibody to IL-6. Furthermore, IL-17RKO mice failed to show the recurrence of stromal keratitis (SK) lesions upon FTY720 withdrawal. These results indicate that approaches such as neutralization of proinflammatory cytokines might be considered along with FTY720 treatment if interruption of drug therapy becomes necessary.
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spelling pubmed-40282162014-05-21 An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy Reddy, Pradeep B. J. Sehrawat, Sharvan Suryawanshi, Amol Rajasagi, Naveen K. Khatri, Madhu Rouse, Barry T. PLoS One Research Article Long-term treatment with the fungal metabolite drug FTY720 (Fingolimod) was shown to be highly effective in controlling viral immunopathological lesions. However, in this report we show that the anti-inflammatory effect of FTY720 in herpes simplex virus-1 (HSV-1) induced ocular inflammation is lost upon the discontinuation of treatment and lesions rapidly recurred. The lesions that developed after FTY720 treatment withdrawal involved mainly Th17 cells rather than Th1 cells explained in part by differential expression of surface CD103, an integrin that permits migration of effector cells to inflammatory sites. The expression of IL-6, a proinflammatory cytokine involved in the generation of Th17 cells, was found to be increased in FTY treated mice as compared to controls and this effect could be abrogated upon administration of neutralizing antibody to IL-6. Furthermore, IL-17RKO mice failed to show the recurrence of stromal keratitis (SK) lesions upon FTY720 withdrawal. These results indicate that approaches such as neutralization of proinflammatory cytokines might be considered along with FTY720 treatment if interruption of drug therapy becomes necessary. Public Library of Science 2014-05-20 /pmc/articles/PMC4028216/ /pubmed/24846129 http://dx.doi.org/10.1371/journal.pone.0098051 Text en © 2014 Reddy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Reddy, Pradeep B. J.
Sehrawat, Sharvan
Suryawanshi, Amol
Rajasagi, Naveen K.
Khatri, Madhu
Rouse, Barry T.
An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy
title An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy
title_full An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy
title_fullStr An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy
title_full_unstemmed An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy
title_short An Approach to Control Relapse of Inflammatory Lesions after Discontinuation of Primary Therapy
title_sort approach to control relapse of inflammatory lesions after discontinuation of primary therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028216/
https://www.ncbi.nlm.nih.gov/pubmed/24846129
http://dx.doi.org/10.1371/journal.pone.0098051
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