The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review
Sepsis-associated lung injury (SALI) is a critical condition with high mortality. Current therapies are limited, necessitating novel approaches. This review highlights the potential of exogenous Specialized Pro-resolving Mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, in m...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1622754/full |
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| author | Jiwei Shen Jiwei Shen Jiwei Shen Huiqin Shen Huiqin Shen Huiqin Shen Shujun Sun Shujun Sun Shujun Sun Shiwen Fan Shiwen Fan Shiwen Fan Tianhao Zhang Tianhao Zhang Tianhao Zhang Guobin Song Guobin Song Guobin Song Ning An Ning An Ning An Xiangdong Chen Xiangdong Chen Xiangdong Chen Yafen Gao Yafen Gao Yafen Gao |
| author_facet | Jiwei Shen Jiwei Shen Jiwei Shen Huiqin Shen Huiqin Shen Huiqin Shen Shujun Sun Shujun Sun Shujun Sun Shiwen Fan Shiwen Fan Shiwen Fan Tianhao Zhang Tianhao Zhang Tianhao Zhang Guobin Song Guobin Song Guobin Song Ning An Ning An Ning An Xiangdong Chen Xiangdong Chen Xiangdong Chen Yafen Gao Yafen Gao Yafen Gao |
| author_sort | Jiwei Shen |
| collection | DOAJ |
| description | Sepsis-associated lung injury (SALI) is a critical condition with high mortality. Current therapies are limited, necessitating novel approaches. This review highlights the potential of exogenous Specialized Pro-resolving Mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, in mitigating SALI. SPMs, derived from polyunsaturated fatty acids, exert protective effects through multiple mechanisms: enhancing alveolar fluid clearance by upregulating ENaC, Na,K-ATPase, CFTR, and AQP5; reducing alveolar epithelial cell apoptosis and epithelial-mesenchymal transition; preserving endothelial glycocalyx integrity via modulating heparanase and exostosin-1 expression; alleviating oxidative stress and mitochondrial dysfunction by scavenging ROS and activating Nrf2; and immunomodulation by limiting neutrophil infiltration, promoting macrophage efferocytosis and M2 polarization, and dampening pro-inflammatory cytokine production. Notably, SPMs like RvD2 remain effective even during sepsis’ immunosuppressive phase. While significant debates persist regarding endogenous SPM generation, receptor mechanisms, and critically the reliable detection and physiological relevance of specific SPMs in biological samples like lung tissue (with earlier reports often misidentifying analytical artifacts or failing LOD/LOQ validation), recent evidence suggests exogenous SPMs act via biased allosteric modulation of the EP4 receptor to stimulate phagocytosis and resolution. Extensive preclinical evidence underscores SPMs’ promise in restoring immune homeostasis in SALI, though pharmacokinetic limitations of high-dose exogenous administration require consideration. Future high-quality clinical trials are essential to translate this resolution pharmacology approach into clinical practice. |
| format | Article |
| id | doaj-art-8bbb54d99c44476d96753b684af46e4d |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-8bbb54d99c44476d96753b684af46e4d2025-08-20T03:58:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16227541622754The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a reviewJiwei Shen0Jiwei Shen1Jiwei Shen2Huiqin Shen3Huiqin Shen4Huiqin Shen5Shujun Sun6Shujun Sun7Shujun Sun8Shiwen Fan9Shiwen Fan10Shiwen Fan11Tianhao Zhang12Tianhao Zhang13Tianhao Zhang14Guobin Song15Guobin Song16Guobin Song17Ning An18Ning An19Ning An20Xiangdong Chen21Xiangdong Chen22Xiangdong Chen23Yafen Gao24Yafen Gao25Yafen Gao26Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaKey Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, ChinaSepsis-associated lung injury (SALI) is a critical condition with high mortality. Current therapies are limited, necessitating novel approaches. This review highlights the potential of exogenous Specialized Pro-resolving Mediators (SPMs), including lipoxins, resolvins, protectins, and maresins, in mitigating SALI. SPMs, derived from polyunsaturated fatty acids, exert protective effects through multiple mechanisms: enhancing alveolar fluid clearance by upregulating ENaC, Na,K-ATPase, CFTR, and AQP5; reducing alveolar epithelial cell apoptosis and epithelial-mesenchymal transition; preserving endothelial glycocalyx integrity via modulating heparanase and exostosin-1 expression; alleviating oxidative stress and mitochondrial dysfunction by scavenging ROS and activating Nrf2; and immunomodulation by limiting neutrophil infiltration, promoting macrophage efferocytosis and M2 polarization, and dampening pro-inflammatory cytokine production. Notably, SPMs like RvD2 remain effective even during sepsis’ immunosuppressive phase. While significant debates persist regarding endogenous SPM generation, receptor mechanisms, and critically the reliable detection and physiological relevance of specific SPMs in biological samples like lung tissue (with earlier reports often misidentifying analytical artifacts or failing LOD/LOQ validation), recent evidence suggests exogenous SPMs act via biased allosteric modulation of the EP4 receptor to stimulate phagocytosis and resolution. Extensive preclinical evidence underscores SPMs’ promise in restoring immune homeostasis in SALI, though pharmacokinetic limitations of high-dose exogenous administration require consideration. Future high-quality clinical trials are essential to translate this resolution pharmacology approach into clinical practice.https://www.frontiersin.org/articles/10.3389/fphar.2025.1622754/fullspecialized pro-resolving mediators (SPMs)sepsis-associated lung injurylipoxinresolvinprotectinmaresins |
| spellingShingle | Jiwei Shen Jiwei Shen Jiwei Shen Huiqin Shen Huiqin Shen Huiqin Shen Shujun Sun Shujun Sun Shujun Sun Shiwen Fan Shiwen Fan Shiwen Fan Tianhao Zhang Tianhao Zhang Tianhao Zhang Guobin Song Guobin Song Guobin Song Ning An Ning An Ning An Xiangdong Chen Xiangdong Chen Xiangdong Chen Yafen Gao Yafen Gao Yafen Gao The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review Frontiers in Pharmacology specialized pro-resolving mediators (SPMs) sepsis-associated lung injury lipoxin resolvin protectin maresins |
| title | The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review |
| title_full | The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review |
| title_fullStr | The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review |
| title_full_unstemmed | The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review |
| title_short | The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review |
| title_sort | potential of exogenous specialized pro resolving mediators in protecting against sepsis associated lung injury a review |
| topic | specialized pro-resolving mediators (SPMs) sepsis-associated lung injury lipoxin resolvin protectin maresins |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1622754/full |
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