Lung-Delivered IL-10 Therapy Elicits Beneficial Effects via Immune Modulation in Organic Dust Exposure-Induced Lung Inflammation

Authors

Aaron D. Schwab, University of Nebraska Medical CenterFollow
Todd A. Wyatt, twyatt@unmc.eduFollow
Amy J. Nelson, University of Nebraska Medical CenterFollow
Angela Gleason, University of Nebraska Medical CenterFollow
Rohit Gaurav, University of Nebraska Medical Center
Debra J. Romberger, University of Nebraska Medical CenterFollow
Jill A. Poole, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Journal of Immunotoxicology

Publication Date

2024

Volume

21

Abstract

Efficacious 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 CD11c^intCD11b⁺ 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 CD11c^intCD11b⁺ 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.

MeSH Headings

Animals, Mice, Swine, Interleukin-10, Mice, Inbred C57BL, Pneumonia, Lung, Lung Diseases, Dust

DOI Link

10.1080/1547691X.2024.2332172

ISSN

1547-6901

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Schwab, Aaron D.; Wyatt, Todd A.; Nelson, Amy J.; Gleason, Angela; Gaurav, Rohit; Romberger, Debra J.; and Poole, Jill A., "Lung-Delivered IL-10 Therapy Elicits Beneficial Effects via Immune Modulation in Organic Dust Exposure-Induced Lung Inflammation" (2024). Journal Articles: Pulmonary & Critical Care Med. 16.
https://digitalcommons.unmc.edu/com_pulm_articles/16