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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 TNF\u03b1- and IFN\u03b3-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 TNF\u03b1, IFN\u03b3 and GM-CSF to boost human PMNs in phagocytosis and direct killing of<jats:italic>C. albicans in vitro<\/jats:italic>. It also down-regulated reactive oxygen production and neutrophil extracellular trap formation by human PMNs stimulated with yeast-derived \u03b2-glucans in the presence of TNF\u03b1, IFN\u03b3 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.<\/jats:p>","DOI":"10.1038\/s41598-017-07261-1","type":"journal-article","created":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T10:40:46Z","timestamp":1500892846000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis"],"prefix":"10.1038","volume":"7","author":[{"given":"Yong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Yuan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Yan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,28]]},"reference":[{"key":"7261_CR1","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1002\/art.38779","volume":"66","author":"S Cohen","year":"2014","unstructured":"Cohen, S. et al. 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