Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation
AbstractEfficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2332172 |
| _version_ | 1797229026792701952 |
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| author | Aaron D. Schwab Todd A. Wyatt Amy J. Nelson Angela Gleason Rohit Gaurav Debra J. Romberger Jill A. Poole |
| author_facet | Aaron D. Schwab Todd A. Wyatt Amy J. Nelson Angela Gleason Rohit Gaurav Debra J. Romberger Jill A. Poole |
| author_sort | Aaron D. Schwab |
| collection | DOAJ |
| description | AbstractEfficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 μg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 treatment reduced ODE (25%, 50%)-induced lung levels of TNFα (–76%, −83% [reduction], respectively), neutrophil chemoattractant CXCL1 (–51%, −60%), and lavage fluid IL-6 (–84%, −89%). IL-10 treatment reduced ODE (25%, 50%)-induced lung neutrophils (–49%, −70%) and recruited CD11cintCD11b+ monocyte-macrophages (–49%, −70%). IL-10 therapy reduced ODE-associated expression of antigen presentation (MHC Class II, CD80, CD86) and inflammatory (Ly6C) markers and increased anti-inflammatory CD206 expression on CD11cintCD11b+ cells. ODE (12.5%, 25%)-induced lung pathology was also reduced with IL-10 therapy. In conclusion, the studies here showed that short-term, lung-delivered IL-10 treatment induced a beneficial response in reducing inflammatory consequences (that were also associated with striking reduction in recruited monocyte-macrophages) following acute complex organic dust exposure. |
| first_indexed | 2024-04-24T15:06:03Z |
| format | Article |
| id | doaj.art-2822d7a139e442fb86e7176047ee803e |
| institution | Directory Open Access Journal |
| issn | 1547-691X 1547-6901 |
| language | English |
| last_indexed | 2024-04-24T15:06:03Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj.art-2822d7a139e442fb86e7176047ee803e2024-04-02T13:14:30ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012024-12-0121110.1080/1547691X.2024.2332172Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammationAaron D. Schwab0Todd A. Wyatt1Amy J. Nelson2Angela Gleason3Rohit Gaurav4Debra J. Romberger5Jill A. Poole6Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USADivision of Allergy and Immunology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USADivision of Allergy and Immunology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USADivision of Allergy and Immunology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USADivision of Allergy and Immunology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USAAbstractEfficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 μg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 treatment reduced ODE (25%, 50%)-induced lung levels of TNFα (–76%, −83% [reduction], respectively), neutrophil chemoattractant CXCL1 (–51%, −60%), and lavage fluid IL-6 (–84%, −89%). IL-10 treatment reduced ODE (25%, 50%)-induced lung neutrophils (–49%, −70%) and recruited CD11cintCD11b+ monocyte-macrophages (–49%, −70%). IL-10 therapy reduced ODE-associated expression of antigen presentation (MHC Class II, CD80, CD86) and inflammatory (Ly6C) markers and increased anti-inflammatory CD206 expression on CD11cintCD11b+ cells. ODE (12.5%, 25%)-induced lung pathology was also reduced with IL-10 therapy. In conclusion, the studies here showed that short-term, lung-delivered IL-10 treatment induced a beneficial response in reducing inflammatory consequences (that were also associated with striking reduction in recruited monocyte-macrophages) following acute complex organic dust exposure.https://www.tandfonline.com/doi/10.1080/1547691X.2024.2332172Organic dusttherapyimmunologyinflammationlung disease |
| spellingShingle | Aaron D. Schwab Todd A. Wyatt Amy J. Nelson Angela Gleason Rohit Gaurav Debra J. Romberger Jill A. Poole Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation Journal of Immunotoxicology Organic dust therapy immunology inflammation lung disease |
| title | Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation |
| title_full | Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation |
| title_fullStr | Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation |
| title_full_unstemmed | Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation |
| title_short | Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation |
| title_sort | lung delivered il 10 therapy elicits beneficial effects via immune modulation in organic dust exposure induced lung inflammation |
| topic | Organic dust therapy immunology inflammation lung disease |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2332172 |
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