Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway
Abstract Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains unclear. The purpose of this study is to establish a septic rat model by cecal ligation and...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12950-023-00332-3 |
| _version_ | 1811171835302117376 |
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| author | Xinxin Zhang Xingsheng Wang Li Sun Guangsheng Gao Yun Li |
| author_facet | Xinxin Zhang Xingsheng Wang Li Sun Guangsheng Gao Yun Li |
| author_sort | Xinxin Zhang |
| collection | DOAJ |
| description | Abstract Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains unclear. The purpose of this study is to establish a septic rat model by cecal ligation and perforation, and to evaluate the effect of tofacitinib on the survival rate of septic rat model and its role in acute lung injury in septic rats and the possible mechanism of action. In this study, TOFA (1 mg/kg, 3 mg/kg, 10 mg/kg) was used to observe the survival rate of septic rats. It was found that TOFA (10 mg/kg) significantly improved the survival rate of septic rats. We selected TOFA (10 mg/kg) and focused on the protective effect of TOFA on acute lung injury. The results confirmed that TOFA significantly inhibited the expression of TNF-α, IL-1β, IL-6 and IFN-γ inflammatory factors, reduced the W/D weight ratio of septic lung tissue, and significantly improved lung histopathological damage. These results may be related to the inhibitory effect of TOFA on JAK-STAT/NF-κ B signaling pathway. In conclusion, for the first time, we found that TOFA has a protective effect against sepsis-induced acute lung injury, and it may be a promising drug for the treatment of acute lung injury in sepsis. |
| first_indexed | 2024-04-10T17:21:50Z |
| format | Article |
| id | doaj.art-9d2ef5a68b2e4d68a3b1fc9912690a61 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-04-10T17:21:50Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-9d2ef5a68b2e4d68a3b1fc9912690a612023-02-05T12:04:49ZengBMCJournal of Inflammation1476-92552023-02-0120111010.1186/s12950-023-00332-3Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathwayXinxin Zhang0Xingsheng Wang1Li Sun2Guangsheng Gao3Yun Li4Department of Emergency Medicine, Fuyang People’s Hospital of Anhui Medical UniversityIntensive Care Unit, Central Hospital Affiliated to Shandong First Medical UniversityDepartment of Health Care, Central Hospital Affiliated to Shandong First Medical UniversityIntensive Care Unit, Central Hospital Affiliated to Shandong First Medical UniversityIntensive Care Unit, Central Hospital Affiliated to Shandong First Medical UniversityAbstract Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains unclear. The purpose of this study is to establish a septic rat model by cecal ligation and perforation, and to evaluate the effect of tofacitinib on the survival rate of septic rat model and its role in acute lung injury in septic rats and the possible mechanism of action. In this study, TOFA (1 mg/kg, 3 mg/kg, 10 mg/kg) was used to observe the survival rate of septic rats. It was found that TOFA (10 mg/kg) significantly improved the survival rate of septic rats. We selected TOFA (10 mg/kg) and focused on the protective effect of TOFA on acute lung injury. The results confirmed that TOFA significantly inhibited the expression of TNF-α, IL-1β, IL-6 and IFN-γ inflammatory factors, reduced the W/D weight ratio of septic lung tissue, and significantly improved lung histopathological damage. These results may be related to the inhibitory effect of TOFA on JAK-STAT/NF-κ B signaling pathway. In conclusion, for the first time, we found that TOFA has a protective effect against sepsis-induced acute lung injury, and it may be a promising drug for the treatment of acute lung injury in sepsis.https://doi.org/10.1186/s12950-023-00332-3SepsisCecum ligation perforationTofacitinibJAK-STATNF-κ B |
| spellingShingle | Xinxin Zhang Xingsheng Wang Li Sun Guangsheng Gao Yun Li Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway Journal of Inflammation Sepsis Cecum ligation perforation Tofacitinib JAK-STAT NF-κ B |
| title | Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway |
| title_full | Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway |
| title_fullStr | Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway |
| title_full_unstemmed | Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway |
| title_short | Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway |
| title_sort | tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the jak stat nf κb pathway |
| topic | Sepsis Cecum ligation perforation Tofacitinib JAK-STAT NF-κ B |
| url | https://doi.org/10.1186/s12950-023-00332-3 |
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