Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets
Abstract Hospital mortality in sepsis varies between 30–45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38311-6 |
| _version_ | 1797778883111550976 |
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| author | Liliana Kiczak Urszula Pasławska Waldemar Goździk Barbara Adamik Marzena Zielińska Stanisław Zieliński Kacper Nowak Michał Płóciennik Jacek Bania Aleksandra Tabiś Marcin Nowak Robert Pasławski Claes Frostell |
| author_facet | Liliana Kiczak Urszula Pasławska Waldemar Goździk Barbara Adamik Marzena Zielińska Stanisław Zieliński Kacper Nowak Michał Płóciennik Jacek Bania Aleksandra Tabiś Marcin Nowak Robert Pasławski Claes Frostell |
| author_sort | Liliana Kiczak |
| collection | DOAJ |
| description | Abstract Hospital mortality in sepsis varies between 30–45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1β maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1β. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1β form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1β processing. |
| first_indexed | 2024-03-12T23:23:56Z |
| format | Article |
| id | doaj.art-170e8aacc706403e94acada707880493 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T23:23:56Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-170e8aacc706403e94acada7078804932023-07-16T11:14:36ZengNature PortfolioScientific Reports2045-23222023-07-0113111210.1038/s41598-023-38311-6Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in pigletsLiliana Kiczak0Urszula Pasławska1Waldemar Goździk2Barbara Adamik3Marzena Zielińska4Stanisław Zieliński5Kacper Nowak6Michał Płóciennik7Jacek Bania8Aleksandra Tabiś9Marcin Nowak10Robert Pasławski11Claes Frostell12Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life SciencesVeterinary Center, Nicoalus Copernicus University in ToruńClinical Department of Anesthesiology and Intensive Therapy, Wrocław Medical UniversityClinical Department of Anesthesiology and Intensive Therapy, Wrocław Medical UniversityClinical Department of Anesthesiology and Intensive Therapy, Wrocław Medical UniversityClinical Department of Anesthesiology and Intensive Therapy, Wrocław Medical UniversityDepartment of Internal Diseases and Clinic of Diseases of Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life SciencesDepartment of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life SciencesDepartment of Food Hygiene and Consumer Health Protection, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life SciencesDepartment of Food Hygiene and Consumer Health Protection, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life SciencesDepartment of Pathology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life SciencesVeterinary Center, Nicoalus Copernicus University in ToruńDepartment of Anesthesia and Intensive Care, Karolinska Institutet Danderyd HospitalAbstract Hospital mortality in sepsis varies between 30–45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1β maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1β. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1β form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1β processing.https://doi.org/10.1038/s41598-023-38311-6 |
| spellingShingle | Liliana Kiczak Urszula Pasławska Waldemar Goździk Barbara Adamik Marzena Zielińska Stanisław Zieliński Kacper Nowak Michał Płóciennik Jacek Bania Aleksandra Tabiś Marcin Nowak Robert Pasławski Claes Frostell Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets Scientific Reports |
| title | Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets |
| title_full | Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets |
| title_fullStr | Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets |
| title_full_unstemmed | Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets |
| title_short | Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets |
| title_sort | effect of low dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in lps induced sepsis in piglets |
| url | https://doi.org/10.1038/s41598-023-38311-6 |
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