A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis

Abstract Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. However, recent evidence suggests that long-term tofacitinib treatment is associated with i...

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Autores principales:	Yong Chen, Fang-Yuan Gong, Zhen-Jun Li, Zheng Gong, Zhe Zhou, Shu-Yan Ma, Xiao-Ming Gao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1597239a30de478b868cebb454176cf8
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spelling	oai:doaj.org-article:1597239a30de478b868cebb454176cf82021-12-02T16:07:02ZA study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis10.1038/s41598-017-07261-12045-2322https://doaj.org/article/1597239a30de478b868cebb454176cf82017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07261-1https://doaj.org/toc/2045-2322Abstract Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. However, recent evidence suggests that long-term tofacitinib treatment is associated with increased risk of infection (e.g. tuberculosis) in patients. In the present study, we illustrate that tofacitinib administration significantly reduced the survival rate of mice given lethal or sub-lethal dose challenge with Candida albicans. This was related to the ability of tofacitinib to reverse TNFα- and IFNγ-enhanced candidacidal activity of murine polymorph nuclear cells (PMNs) and also to suppress chemokine CXCL5 expression and PMN infiltration in the infected tissues of mice. More importantly, tofacitinib significantly antagonized the ability of TNFα, IFNγ and GM-CSF to boost human PMNs in phagocytosis and direct killing of C. albicans in vitro. It also down-regulated reactive oxygen production and neutrophil extracellular trap formation by human PMNs stimulated with yeast-derived β-glucans in the presence of TNFα, IFNγ or GM-CSF. Our data emphasizes a significantly increased risk for opportunistic fungal infection associated long-term tofacitinib treatment in humans, likely through antagonizing the PMN-boosting effect of pro-inflammatory cytokines.Yong ChenFang-Yuan GongZhen-Jun LiZheng GongZhe ZhouShu-Yan MaXiao-Ming GaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yong Chen Fang-Yuan Gong Zhen-Jun Li Zheng Gong Zhe Zhou Shu-Yan Ma Xiao-Ming Gao A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis
description	Abstract Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. However, recent evidence suggests that long-term tofacitinib treatment is associated with increased risk of infection (e.g. tuberculosis) in patients. In the present study, we illustrate that tofacitinib administration significantly reduced the survival rate of mice given lethal or sub-lethal dose challenge with Candida albicans. This was related to the ability of tofacitinib to reverse TNFα- and IFNγ-enhanced candidacidal activity of murine polymorph nuclear cells (PMNs) and also to suppress chemokine CXCL5 expression and PMN infiltration in the infected tissues of mice. More importantly, tofacitinib significantly antagonized the ability of TNFα, IFNγ and GM-CSF to boost human PMNs in phagocytosis and direct killing of C. albicans in vitro. It also down-regulated reactive oxygen production and neutrophil extracellular trap formation by human PMNs stimulated with yeast-derived β-glucans in the presence of TNFα, IFNγ or GM-CSF. Our data emphasizes a significantly increased risk for opportunistic fungal infection associated long-term tofacitinib treatment in humans, likely through antagonizing the PMN-boosting effect of pro-inflammatory cytokines.
format	article
author	Yong Chen Fang-Yuan Gong Zhen-Jun Li Zheng Gong Zhe Zhou Shu-Yan Ma Xiao-Ming Gao
author_facet	Yong Chen Fang-Yuan Gong Zhen-Jun Li Zheng Gong Zhe Zhou Shu-Yan Ma Xiao-Ming Gao
author_sort	Yong Chen
title	A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis
title_short	A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis
title_full	A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis
title_fullStr	A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis
title_full_unstemmed	A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis
title_sort	study on the risk of fungal infection with tofacitinib (cp-690550), a novel oral agent for rheumatoid arthritis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1597239a30de478b868cebb454176cf8
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A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis

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