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Therapeutic Effects of Intranasal Tofacitinib on Chronic Rhinosinusitis with Nasal Polyps in Mice
Author(s) -
Joo YeonHee,
Cho HyunJin,
Jeon Yung Jin,
Kim Jin Hyun,
Jung Myeong Hee,
Jeon SeaYuong,
Suh Young Sun,
Park Jung Je,
Kim SangWook
Publication year - 2021
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.29129
Subject(s) - tofacitinib , medicine , janus kinase , eotaxin , immunology , eosinophil , nasal polyps , stat , nasal administration , eosinophilic , chemokine , inflammation , pharmacology , cytokine , signal transduction , pathology , rheumatoid arthritis , stat3 , biology , biochemistry , asthma
Objectives The Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP). Methods An eosinophilic CRSwNP model was induced using 4‐week‐old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA‐3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL‐4, IL‐5, IL‐12, and interferon‐γ, were measured using enzyme‐linked immunosorbent assays (ELISA). Results Topical tofacitinib administration significantly reduced the number of polyp‐like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA‐3. Lastly, tofacitinib significantly decreased IL‐4 and IL‐5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon‐γ. Conclusion Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs. Level of Evidence N/A. Laryngoscope , 131:E1400–E1407, 2021