Inhalative IL-10 treatment after bilateral femoral fractures affect pulmonary inflammation in mice

Abstract

Background: Musculoskeletal injuries induce systemic inflammation which often impairs lung function contributing to morbidity. IL-10 has been shown to have a beneficial effect on immune dysfunction and organ damage after different traumatic insults. We sought to investigate the effect of inhalative IL-10 administration on the systemic and pulmonary inflammatory response in a small animal model of bilateral femoral fracture.

Materials and methods: Male C57/BL6 mice (6 animals per group) were subjected to bilateral femoral fracture and intramedullary nailing followed by inhalative administration of either 50μL PBS (Fx group) or 50μg/kg recombinant mouse IL-10 dissolved in 50μL PBS (FxIL-10 group). All animals were sacrificed at 6, 24, or 72h after fracture induction. Blood samples were collected and analyzed for IL-6, IL-10, KC, and MCP-1 (CCL2) plasma concentrations by Bio-Plex Pro™ assays. Pulmonary infiltration by neutrophils was assessed by myeloperoxidase (MPO) activity (ELISA) and histological analysis of lung tissue. Pulmonary ICAM-1 expression (immunohistochemistry), and pulmonary IL-6 levels (ELISA) were determined.

Results: Inhalative IL-10 administration showed a decrease in the pulmonary infiltration by neutrophils. A significant decrease in the expression of the adhesion molecule ICAM-1 after local IL-10 application was observed. In contrast, local IL-10 administration did not show a significant effect on the systemic inflammatory response.

Conclusion: Our findings suggest that inhalative IL-10 administration may beneficially modulate the pulmonary microenvironment, in which IL-10 effect on the local ICAM-1 expression seems to play a central role.

Keywords: Fracture; Inflammation; Inhalative IL-10; Mouse model.